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On the main panel, the chosen layout (10–10, 10–5 EEG_32 or 10–5 EEG_64 – Methods section) will be depicted and automatically populated with sources (red) and detectors (blue) optodes following chosen mode, parcellation method, anatomical landmarks and minimum specificity threshold.
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other
| 99.9 |
By clicking on the “Summary” tab, the user can access most relevant information about the created optodes arrangement. As illustrated in Fig. 8, the information is summarized in three different sub-tabs: (i) Landmarks, (ii) Channels, and (iii) Sources and Detectors. The first presents information of all channels generated for a given landmark of interest, similar as shown in Table 3. ‘Channels’ will display a table with formed channels and list of landmarks covered by each of them, similar as in Table 2. The last tab (‘Sources and Detectors’) presents a list of sources and detectors required and sorted by the number of channels formed.Figure 8Illustration of further tabs available under “Summary”. ‘Landmarks’ (top), ‘Channels’ (center) and ‘Sources and Detectors’ (bottom), each of them presenting tables with summarized information about the fNIRS optode layout designed.
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other
| 94.5 |
In addition to the choice of anatomical landmarks based on parcellation atlases, one can also switch the working mode to “Image Mask”, by clicking on “Mode: Parcellation”. This will pop up a message dialog to the user informing the switching to “Image Mask” and, if accepted to proceed, the user will be prompted to choose a NIfTI or ANALYZE file.
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other
| 99.94 |
The selected image file will be loaded in the toolbox, resampled to 2 × 2 × 2 mm3, and the toolbox will look for any overlap of its voxels presenting values greater than 0 with those of each fNIRS channel extent. For each channel, the specificity to the loaded region of interest will be calculated (Equation 3) and the optodes related to channels surviving the minimum specificity threshold will be displayed in the main panel.
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other
| 90.3 |
Figure 9 illustrates an example of NIfTI file representing the posterior temporal- parietal junction (pTPJ) loaded in “Mode: Image Mask” and resulted on a channel CP6-P6 given the set minimum specificity threshold of 20%. The same figure also illustrates an axial view of the Colin27 segmented head with overlays of the pTPJ NIfTI file and the normalized sensitivity (Methods section) of the channel CP6-P6, showing their overlap. It is interesting to note that the positions yielding a greater spatial specificity to the pTPJ did not coincide with the usual choice of international positions labeled as “TP” (temporal-parietal).Figure 9Representative NIfTI file for posterior temporal-parietal junction (pTPJ) as obtained from Archive of Neuroimaging Meta-Analyses (ANIMA)50 and published by Bzdok et al.53. was loaded in the fOLD toolbox in the ‘Image Mask’ Mode, (A) resulting on channel formed by positions CP6 and P6. (B) Overlay of pTPJ (in violet) on Colin27 segmented atlas with an additional overlay of sensitivity for channel CP6-P6.
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study
| 100.0 |
Representative NIfTI file for posterior temporal-parietal junction (pTPJ) as obtained from Archive of Neuroimaging Meta-Analyses (ANIMA)50 and published by Bzdok et al.53. was loaded in the fOLD toolbox in the ‘Image Mask’ Mode, (A) resulting on channel formed by positions CP6 and P6. (B) Overlay of pTPJ (in violet) on Colin27 segmented atlas with an additional overlay of sensitivity for channel CP6-P6.
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study
| 99.94 |
In “Mode: Image Mask”, the options available under “Brain Atlas” are not related to the parcellation atlases anymore, but rather to the head segmented atlases Colin27 and SPM12 (Methods section). Also, next to “Anatomical Landmarks”, the user can load further images to be included in the landmarks list for more robust creation of fNIRS optodes arrangement from NIfTI or ANALYZE files.
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other
| 99.9 |
The toolbox incorporates the overlapping results obtained from the anatomical landmarks from five different parcellation methods (Methods section), while it also allows the user to load an image file of interest to be used as mask for the positions definition (Toolbox section and Fig. 9).
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other
| 99.9 |
Output results of the toolbox are presented on the reference cap layout of interest (10–10, 10–5_EEG-32 or 10–5_EEG-64 – Methods section), as well as in summarizing tables. The tables provide summarized information on anatomical landmarks’ (ROI) specificity (equation 2), channels’ MNI coordinates (equation 3) and number of channels per optode (Fig. 8). The summary information can also be exported to Excel sheets (*.xls) and to text files (*.txt), as described in Toolbox section.
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other
| 99.44 |
The current version presents following limitations: (I) the resulting channels can only be formed either for positions based on 10–10 or 10–5 extent, i.e. one cannot combine them into a single layout; (II) high-density arrangements for 3D diffuse optical tomography43,44 cannot be automatically generated from within fOLD; (III) the normalized sensitivity is separately calculated on a channel basis and does not accumulate for near channels with eventual overlapping photon transport. These first three limitations mainly concern the possibility of extending the presented approach to appreciate the potential for tomography studies, while the current version of fOLD rather focuses on topography (i.e. in the absence of major overlap of sensitivity profiles of photon transport). Nevertheless, we believe that one can potentially identify the most relevant positions from within fOLD and extend its output to a higher-density of optodes by placing more channels around the retrieved topographical positions.
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study
| 100.0 |
Additionally, further limitations concern the implemented methodology: (A) the photon transport simulations have been generated with two distinct head atlases (Colin27 and SPM12), whose tissues’ geometries (e.g. scalp and skull thickness) may significantly differ from other adult individuals27; (B) our results should only be valid for adults, as we did not consider head atlases for children or infants45; (C) there is seemingly no gold standard on values for tissues’ optical properties, as recent studies based on photon transport simulations applied different values from one another27,30,31,46; (D) the fiducials points for each head atlas have been visually identified, while it has been shown that the visual identification of inion may be ambiguous12,47; (E) different tissue segmentation methods available may yield different thickness results48, although SPM12 has not been assessed yet; (F) the results provided as output of the toolbox are restricted to the 10–10/10–5 international systems positions12.
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study
| 100.0 |
Also, due to the predefined potential positions for the optodes as based on the international systems (10–10 and 10–5), the resulting inter-optode distance is not constant for the resulting channels. Nevertheless, to avoid too long distances that could not provide measurements with a proper signal-to-noise ratio, we only considered channels formed by neighboring optical positions on 10–10 or 10–5. This yielded a median inter-optode distance of 3.60 cm, while the upper quartile is 3.98 cm and the lower quartile is 3.13 cm. There are only five possible channels that exceed 4.50 cm (two from 10–10 and three from 10–5). Given proper headgear preparation and detected signal amplification, we envision that fNIRS users can obtain reasonable signal-to-noise ratio with the channels output of the toolbox.
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study
| 94.2 |
In the context of previously proposed methods to address the definition of optodes position for fNIRS to target a set of brain regions-of-interest9–11, the main feature differentiating our method and developed toolbox is its simplification and consequent accessibility. The simplification relies on the fact that fOLD does not require digitalization of optodes positions nor individual structural scans, and the results of photon transport simulations have been computed offline and are readily available within the toolbox. Additionally, the accessibility of the method could be achieved by considering the 10–10 and 10–5 international systems as references for optodes arrangement and by relying on head atlases as templates for photon transport simulations. Thus, fOLD can be accessed and used by groups with different levels of expertise and background, while it does not require additional hardware (digitizer and MR scanner), nor further photon transport simulations. Nevertheless, the results are obtained independently of anatomic variances between-subjects, and it requires the optodes to be precisely placed in accordance to the international systems12. In agreement with the conclusions presented by Machado et al.9, we believe that these simplifications are acceptable for fNIRS non-clinical applications. Also, Wijeakumar et al.10 had reported significant correlation of the results obtained for subject-specific and head atlas in adults. Finally, using head atlases as templates facilitates both the application of brain parcellation atlases (Methods section) and the fNIRS positions definition based on meta-analyses (Toolbox section), as the latter was also envisioned by Wijeakumar et al.10 as a future approach to identify ROIs.
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study
| 99.94 |
In future versions of fOLD, we intend to include: (1) the possibility to display lines between sources and detector positions to illustrate the formed channels; (2) an optimization algorithm to find the best positions for a given number of sources and detectors; (3) a threshold for the source-detector distance; and (4) an additional threshold metric based on the brain sensitivity (Equation 1) to also assist on the choice of channels that present a higher sensitivity to the brain. We envision that the brain sensitivity information could provide a better prediction on the signal-to-noise ratio of a given channel following removal of extracortical components from its time series. Channels with lower brain sensitivity have a lower portion of cortical components and thus one can expect a lower signal-to-noise ratio in respect to the extracortical signals. Nevertheless, while this has not yet been incorporated into fOLD, it is provided within the supplementary datasets. Also, given that one is capable of properly retrieving the cortical component from the measured channel, for example by including short-distance channels to measure the extracortical changes49, we expect the currently provided threshold of specificity to best represent the portion of region-of-interest covered, regardless the sensitivity to the brain.
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study
| 100.0 |
To conclude, we consider that the presented toolbox is a first-order approach to bring the achieved advancements within fMRI concerning parcellation methods (Methods section) and meta-analyses50–52 to the fNIRS optode positions selection. While it is known that the fNIRS spatial resolution is lower than fMRI, it is possible to increase the precision of hypothesis-driven experimental design by finding the overlapping regions of interest with the simulated fNIRS sensitivity profiles, as illustrated in Fig. 9 based on the meta-analysis of posterior temporal parietal junction53. We envision that the toolbox shall not only benefit the design of fNIRS experiments and optode positions but also improve the discussion of fNIRS results in face of a priori expectation of channels to present a greater anatomical specificity to a region of interest. Finally, the proposed MNI coordinates (Equation 3) calculated from the weighted mean, based on a given channel’s normalized sensitivity, may also further improve results comparison with fMRI and enable fNIRS meta-analyses.
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study
| 99.94 |
The fOLD toolbox is provided as standalone version for Windows (*.exe) or as App package for Matlab. The App package is compatible with Windows, Mac or Ubutu, but currently only for Matlab2017a. The most recent version of fOLD is available in the following GitHub public repository: https://github.com/nirx/fOLD-public.
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other
| 99.94 |
Glaucoma is a major public health challenge, being the leading cause of irreversible blindness worldwide. It has been estimated that 60.5 million people were affected by primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) globally in 2010.[1–4]
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review
| 99.56 |
Elevated intraocular pressure (IOP) is the most important modifiable risk factor associated with glaucoma development. Many experimental studies have demonstrated sustained intraocular pressure reduction after routine cataract extraction in eyes with or without ocular hypertension or glaucomatous disease.[6–8] So far, the mechanism remains poorly understood and the magnitude of this effect is highly variable and unpredictable. In patients with narrow angles, the IOP-lowering effect appears to also be proportional to the degree of anterior chamber angle deepening induced by cataract surgery. However, for POAG, the mechanism is not as clear. Many studies have focused on the relationship between the ocular anatomy and IOP reduction after phacoemulsification. Anterior chamber and angle parameters have been found to be predictive factors. For example, the ratio of the preoperative IOP and anterior chamber depth (ACD)—the pressure-to-depth ratio (PD ratio)—and changes in angle opening distance (AOD) have been reported to be associated with IOP reduction after phacoemulsification in non-glaucoma subjects.
|
review
| 99.7 |
Lens position (LP)—defined as LP = ACD + 1/2 lens thickness (LT)—and relative lens position (RLP)—defined as RLP = LP/axial length are more easily computed from measurements obtained through optical ocular biometry, which is part of routine testing for intraocular lens (IOL) power calculations prior to cataract surgery. They could also be used to understand how the lens affects the IOP reduction seen in previous studies. Our former research found that the percentage of IOP reduction after cataract surgery in non-glaucomatous eyes with open angles is greater in patients with more anteriorly positioned lenses. In addition, we have also shown that LP is an accessible predictor with considerable predictive value for postoperative IOP change.
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study
| 100.0 |
Another area in which LP may be helpful is the understanding of the risk factors and possible treatment for PACG. Progressive shallowing of the anterior chamber (AC) in predisposed eyes is mostly attributable to age-related increase in lens thickness and more anterior positioning of the lens. The restoration of a deeper angle configuration by removing a thickened and anteriorly positioned lens may be advantageous in eyes with PACG and may lead to a significant IOP reduction. Furthermore, differences in ocular anatomy may contribute to ethnic differences in glaucoma risk, particularly for PACG. Previous studies showed that a more anterior lens is related to higher risk for angle closure.[18–20]
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study
| 99.7 |
In this study, we compare the LP and other lens parameters among White, Asian, Hispanic and African-American subjects. We hypothesize that LP is significantly different among ethnicities that are at different risk for developing PACG and that they may respond differently in terms of IOP change after cataract surgery.
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study
| 100.0 |
This retrospective, cross-sectional study was approved by the University of California, San Francisco (UCSF) Committee on Human Research, and the study adhered to the tenets of the Declaration of Helsinki. Due to the retrospective nature of the study, and since the data were analyzed anonymously, UCSF Committee on Human Research determined that it was not necessary to obtain the participants' consent. This study enrolled consecutive subjects who met the inclusion criteria and underwent cataract surgery at the UCSF general ophthalmology and subspecialty clinics between January 1, 2014, and January 31, 2016.
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study
| 99.94 |
The ethnicities of study participants included were White, Asian, Hispanic and African-American. Ethnicity was assessed by self-report. The Asian cohort included individuals of self-reported Chinese, Japanese, Korean, Filipino, and Vietnamese descent. The White cohort included only those of European-derived ancestry. Inclusion criteria included: 1) adult patients (18 years or older); 2) self-reported White, Asian, African-American, or Hispanic ethnicity; and 3) optical biometry with the Lenstar (model LS 900, Haag-Streit AG, Koeniz, Switzerland) prior to planned cataract surgery. Exclusion criteria included
|
study
| 100.0 |
1) self-reported biracial ancestry; 2) uveitis, severe retinal disease such as wet macular degeneration, or congenital anomalies; 3) history of ocular trauma or any prior intraocular surgery; 4) history of intraocular laser treatment; 5) use of steroid or glaucoma drops within the 3 months prior to optical biometry; 6) contact lens use; or 7) inability to conduct the necessary testing. Both eyes of the patients with cataracts were included in the study if they met the inclusion and exclusion criteria. However, not all the eyes underwent cataract surgery after the measurement. In reviewing the medical charts, we ensured that all eyes included in the study were eligible based on inclusion and exclusion criteria. Mixed effects regression modeling was used to adjust for the use of both eyes in some subjects.
|
study
| 100.0 |
The study participants underwent ophthalmologic examinations, including visual acuity assessment, refractometry, keratometry, intraocular pressure measurement by Goldman applanation tonometry, slit-lamp biomicroscopy, and optical biometry which provided data on axial length (AL), anterior chamber depth (ACD), lens thickness (LT), and central corneal thickness (CCT). We conducted optical biometry with the Lenstar. Five readings were taken for each eye, and after omitting the highest and lowest values, the mean of the remaining three readings was used for analysis. All measurements were done for both eyes of all subjects. All enrollees received an ophthalmic examination that included refraction. Trained ophthalmic technicians (R.I.C. and D.T.B.) performed all scans.
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study
| 100.0 |
We used descriptive analyses for the demographic data related to the ethnic cohorts. Nonparametric Wilcoxon rank-sum tests were used to compare cohorts regarding LP, RLP, CCT, LT, and AL. We used linear mixed-effect models to compare differences in LP and RLP between ethnic cohorts while accounting for each eye as a separate entity to maximize the effect of randomization plus including both eyes for analysis. Two-tailed P value <0.05 was deemed statistically significant. All statistical analyses were conducted using Stata version 14.0 (Stata Corp LLP, College Station, TX, USA).
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study
| 100.0 |
Over the study period, there were a total of 2173 eyes assessed using Lenstar optical biometry. Four hundred and fifty-six eyes were excluded because of missing ethnicity information, self-reported biracial ancestry, or ethnicity other than the 4 major groups included in this study; 246 were excluded because of their history of glaucoma; and 110 were excluded because of history of surgery or other eye diseases. After these exclusions, a total of 807 patients and 1361 eyes were included in the study. There were 729 White, 386 Asian, 141 Hispanic and 105 African-American eyes. There were 60.3% women and the mean age of the sample was 69.2 ± 12.7 years. Distribution of laterality was 49.7% right eyes.
|
study
| 100.0 |
Table 1 shows the comparison of the demographic and clinical characteristics of the ethnic cohorts. The mean LP measurements were 5.54 ± 0.32 mm for Whites (largest), 5.38 ± 0.32 mm for Asians, 5.32 ± 0.30 mm for Hispanics (smallest) and 5.40 ± 0.28 mm for African-Americans. The mean RLP measurements were 0.230 ± 0.010 for whites, 0.222 ± 0.010 for Asians, 0.224 ± 0.010 for Hispanics and 0.224 ± 0.010 for African-Americans.
|
study
| 100.0 |
The univariate linear analysis showed that age, sex and AL were potential confounders with LP. The differences between each ethnicity's LP and RLP and those of the reference group (White) are depicted in Tables 2 and 3, respectively. Using a multivariable linear mixed-effect regression model with Whites as the comparator, adjusted for age, sex and AL, we found that significant differences exist compared to the LP in the Asian group (β coefficient = -0.14, 95% CI, -0.18 to -0.09, P<0.001), African-American group (β coefficient = -0.11, 95% CI, -0.18 to -0.04, P = 0.003) and Hispanic group (β coefficient = -0.16, 95% CI, -0.22 to -0.10, P<0.001). Thus, all other races had smaller LP than Whites. The biggest differences were seen in Hispanics and Asians compared to Whites (P<0.001).
|
study
| 100.0 |
Comparison of RLP using multivariable linear mixed-effect regression model, adjusted for age, sex and AL, using White as the reference group, showed that a significant different of RLP exists between ethnic cohorts. The highest negative effects (estimated difference) were seen in Hispanics (coefficient = -0.0062, 95% CI, -0.88 x10-2 to -0.36 x10-2, P<0.01) and after that in Asians (coefficient -0.0055, 95% CI, -0.72 x10-2 to -0.37 x10-2, P<0.01) as compared to White and the lowest negative effect (estimated difference) was seen in African-Americans as compared to White (coefficient = -0.0046, 95% CI, -0.76 x10-2 to -0.16 x10-2, P = 0.002).
|
study
| 100.0 |
Running our multivariable linear mixed-effects regression model test, comparing LP and RLP but using Asians as the baseline, we found significant differences when comparing Asians to African-Americans, White and Hispanic. As a result, we found the lowest values (highest negative effect) of LP and RLP in Hispanics and after that group in Asians while comparing the ethnic cohorts.
|
study
| 100.0 |
Furthermore, pairwise comparison of LT showed that Asians significantly differed from both African-Americans (P<0.001) and Whites (P = 0.001) but not Hispanics (Table 4). We also found that Asians had the thickest LT and African-Americans had the thinnest (Table 1).
|
study
| 100.0 |
In the present study of a convenience sample of patients scheduled to have cataract surgery, using linear mixed-effect regression models, we found Hispanics have the smallest LP and RLP and Asians have the second smallest LP and RLP while having the greatest lens thickness (LT) value (Table 1). The LP of Whites was greater than all other racial groups (P<0.05 for all comparisons) and the RLP was greater than other races as well. Our findings may help provide anatomic insight into the relative risk for PACG among different ethnic groups and the potential efficacy of cataract surgery on IOP in these different groups.
|
study
| 100.0 |
Angle-closure glaucoma is an anatomical disorder of the anterior segment of the eye characterized by permanent closure of part of the filtration angle. Demographic and anatomical factors play significant roles in the development of angle-closure glaucoma.[21–23] Ethnicity was recognized as a major risk factor for primary angle-closure glaucoma in a comprehensive review of the literature conducted by Congdon et al in 1992, with Asians among those with the highest risk and Whites having substantially lower risk. Previous studies have also shown that greater lens thickness (LT), smaller anterior chamber depth (ACD), and shorter axial length (AL) are risk factors for PACG.[25–29] Recent studies have also shown that LP, RLP, and LT can be predictive for angle closure.[30–32] In this current study of a clinic population, our findings suggest that the position and thickness of a lens may also be significantly different among ethnic groups and help explain the differential risk for angle closure among these groups. Hispanics and Asians had the smallest LP and RLP and the thickest LT among the four major racial groups in our study.
|
study
| 99.94 |
Asians have the highest prevalence of PACG.[33–35] Furthermore, a population-based study by Quigley et al. reported that 0.1% of their Hispanic population were affected with PACG. However, it has been speculated that angle closure might be more common among Hispanic individuals in the Western Hemisphere because of their linked heritage to migrants from Asia during the last Ice Age. Sakata K et al. found that PACG was more common among south Brazilians (Hispanic) than in European populations, and the adjusted prevalence of PACG observed in the study suggested that the prevalence of this disease in non-Asian, such as Hispanic, populations may be greater than has been traditionally believed and that most cases are asymptomatic. Interestingly, in our study, the highest LP was recorded in the White group and the lowest measurement was recorded in the Hispanic group. In Whites, these findings are consistent with the low rate of PACG in this group.
|
study
| 99.94 |
However, there have not been any prior studies describing the differences in LP, RLP, and LT among the major major racial groups. Differences in lens position, thickness, and anterior chamber depth in different racial groups and the continued growth of the lens throughout life may be partially responsible for the dissimilarity in the presenting demographic features of patients with PACG.
|
study
| 99.94 |
In 1970, Lowe et al. found that the eyes with chronic ACG are smaller than normal eyes, and the lens is situated relatively more anteriorly in the eye when compared with the lens position in matched normal eyes. We also found that there is a significant relationship between LP and age (and thus, we included the age in the mixed effects regression model as confounder), which means the lens is closer to the cornea as age increases. This substantiates findings in previous studies. According to the iris-lens canal theory, the more anteriorly the lens is positioned, the more likely it is to result in “partial pupillary block.” The posterior chamber–anterior chamber pressure gradient is inversely proportional to the height of the iris-lens canal. When the lens is more anteriorly positioned and the height is decreased, the higher pressure gradient will cause a situation similar to pupillary block.
|
study
| 100.0 |
In our previous study, we found that LP was an accessible parameter with considerable predictive value for postoperative IOP change after cataract surgery in non-glaucomatous patients with open angles. We also found that there is a trend towards a similar effect in POAG eyes. The results of the present study therefore suggest that Asians and Hispanics may benefit more from cataract surgery in terms of IOP control.
|
study
| 100.0 |
One prominent advantage of this study was the use of the Lenstar LS 900 for ocular biometry, a device which has been shown to have high accuracy and can measure CCT, ACD, LT and AL, in addition to keratometric (K) readings and corneal diameter (CD). This machine measures AL from the surface of the cornea (epithelium including the tear film) to the macular pigmentary epithelium and ACD from the surface of the cornea to the anterior surface of the crystalline lens (Fig 1). Shammas et al. reported that the precision of the measurements obtained by the Lenstar was extremely high.
|
study
| 100.0 |
The primary limitation of this study is the use of retrospective data from a convenience sample of subjects scheduled to have cataract surgery at UCSF. However, this feature should not necessarily bias the results in any particular direction such that certain racial groups would have greater likelihood of smaller or greater LP, RLP, and LT. Furthermore, we adjusted for potential confounding factors such as age, gender, and axial length when appropriate. Additional limitations of this study include the relatively small sample size in some groups, investigating lens parameters among cataract surgery population, and the self-reported nature for ethnicity in our study. Moreover, each ethnic group included in this study also has substantial intragroup differences. Self-identification within an ethnic group also does not preclude genetic contribution from another ethnic group. To minimize intra-ethnic variation, we excluded individuals of biracial ancestry. However, it is possible that there is still great genetic diversity within each cohort. Furthermore, this is a retrospective study and parameters from procedures such as gonioscopy and ASOCT were not consistently available. Although IOP is available, we did not evaluate this factor as an outcome because it was assessed by different technicians and devices and at various times of the day, without a fixed protocol.
|
study
| 100.0 |
In summary, we found significant differences in the lens position and relative lens position among various ethnic groups, with Whites having the greatest LP and RLP. In addition, Hispanics followed by Asians had the smallest LP and RLP. These findings may have relevance as to the relative risk for ACG in these groups and potentially in the IOP outcome after cataract surgery. Our results can serve as a starting point for designing future prospective observational studies which have larger populations and a variety of ethnicities.
|
study
| 100.0 |
Edema or swelling of an affected hand is often observed in patients with post-stroke hemiplegia. The incidence of hand edema varies from 9 to 80%, depending on the study’s definitions and measurements [1–3]. One of the causes of hand edema is obstructed venous return . Post-stroke edema has been attributed to impaired functioning of the venous return and lymphatic system as a result of immobility . Persistent hand edema is associated with pain and fibrotic tissue , resulting in an unfavorable effect on hand function. These conditions may even lead to permanent loss of upper limb function. Therefore, the treatment to reduce hand edema is important for maintaining upper limb function in patients with stroke.
|
review
| 99.75 |
In previous studies, treatments for alleviating edema included intermittent compression , upper limb elevation , wrist orthosis , continuous passive motion , and the use of kinesio tape , but their effects were limited. It therefore became apparent that novel, more effective interventions for post-stroke hand edema were required. Recently, Ishii et al. reported that the deoxy-hemoglobin of non-exercising upper limb muscles in 13 healthy men decreased during contralateral one-armed cranking exercise. The direction of changes in deoxy-hemoglobin is determined by changes in the venous blood volume . Hence, Ishii et al.’s results suggested that venous return might be promoted in the affected hand by contralateral hand exercise.
|
study
| 99.9 |
We hypothesized that contralateral venous blood volume increases according to non-affected hand exercise and can be measured by US. The purpose of the present study was to examine, using US, the effect of handgrip exercise by the non-affected hand on the venous return in the affected upper limb in patients with stroke. The present study’s results could have consequences for the development of a new intervention for post-stroke hand edema based on venous return.
|
study
| 100.0 |
Seven men (mean age 60 years, range 44–73 years) within 6 months of their unilateral first-ever stroke participated in the study. All patients were admitted to the post-acute rehabilitation unit of Gifu Central Hospital or Tokai Memorial Hospital in Japan. Patients with severe cognitive impairment and those with cardiac pacemakers were not included in the study. The study protocol, which met the standards of the Declaration of Helsinki, was approved by the research ethics committees of Seijoh University (Approval Number 2016C0022), Gifu Central (Approval Number 133), and Tokai Memorial Hospital. Informed written consent was obtained from each participant before all procedures. All experiments were performed in a soundproof room in which the temperature was maintained at 24–26 °C.
|
study
| 100.0 |
All examinations were performed on the axillary vein of the affected side with the patient in supine position and the arms kept alongside the body. The diameter and flow velocity of the axillary vein in the affected upper limb was measured using a Xario US device (Toshiba Medical Systems, Tokyo, Japan) with a 7.5-MHz linear probe. Accurate identification of the vein was confirmed by a positive compressive pressure test and by assessing venous flow via color Doppler imaging.
|
clinical case
| 99.5 |
Doppler spectra for calculating the time-averaged mean velocity (cm/s) was obtained in a longitudinal plane at the same site with an insonating angle maintained at < 60°. The sample volume was positioned at the center of the vessel, and the amplitude was adjusted to allow sampling of 50–70% of the vessel lumen .
|
study
| 99.94 |
Using the obtained data, we calculated the venous flow volume (ml/min) in the axillary vein using the following equation:\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ {\text{Venous}}\,{\text{flow}}\,{\text{volume}}\left( {{\text{ml}}/\hbox{min} } \right) = {\text{radius}}\left( {\text{mm}} \right) \times {\text{radius}}\left( {\text{mm}} \right) \times\uppi \, \left( {{\text{circular}}\,{\text{constant}}} \right) \times {\text{time}} - {\text{averaged}}\,{\text{mean}}\,{\text{velocity}}\left( {{\text{cm}}/{\text{s}}} \right) \times 60/100. $$\end{document}Venousflowvolumeml/min=radiusmm×radiusmm×πcircularconstant×time-averagedmeanvelocitycm/s×60/100.
|
study
| 99.94 |
A digital handgrip dynamometer (Takei Scientific Instruments Co., Ltd., Niigata, Japan) was used to measure the maximum grip strength of the non-affected hand of each patient. Grip strength (kg) was measured and recorded as the average of two repetitions. Following the measurement of grip strength, participants were allowed rest breaks of at least 10 min in supine position.
|
study
| 99.9 |
The diameter and flow velocity of the axillary vein on the affected side were measured during two distinct regimens: baseline (rest) or rhythmic resistance exercise (30% of maximum grip strength for 20 s with the movement guided by a metronome at a pace of 1 s/cycle). After a rest period, the diameter (mm) and time-averaged mean velocity (cm/s) were measured as baseline data. Following these measurements, the same parameters were measured during rhythmic resistance exercise. During the handgrip exercise, subjects were told to maintain normal breathing. Each US measurement lasted 15 s.
|
study
| 100.0 |
Paired t-tests were performed to detect the significance of the differences between the baseline values and those measured during the rhythmic resistance exercise for the dynamometer readings, time-averaged mean velocity, and venous flow volume in the axillary vein; blood pressure; and heart rate. In addition, the effect sizes (Cohen’s d) were calculated between the two regimens. All statistical analyses were performed with HAD version 16 software . A value of p < 0.05 was considered to indicate statistical significance. The effect size was calculated with Cohen’s “d” method, where d = 0.2 indicated a small effect, d = 0.5 a medium effect, and d = 0.8 a large effect.
|
study
| 100.0 |
The baseline and rhythmic resistance data are shown in Table 1. There was no significant difference in the venous diameters between the baseline and rhythmic resistance exercise values. In contrast, there was a significant increase in the time-averaged mean velocity during resistance exercise compared with baseline. There was also a significant increase in the venous flow volume during resistance exercise compared with baseline. For the time-averaged mean velocity and venous flow volume, there was not only a significant difference between baseline and resistance exercise but the effect size was moderate.Table 1Venous hemodynamic measurements using ultrasound at baseline and during resistance exerciseMeasurementBaselineResistance exercisep d Venous diameter (mm)6.70 ± 2.726.82 ± 2.640.50− 0.05Time-averaged mean velocity (cm/s)2.66 ± 1.233.99 ± 2.050.01− 0.80Venous flow volume (ml/min)52.35 ± 31.5977.82 ± 38.150.01− 0.74Systolic blood pressure (mmHg)120.86 ± 14.10126.00 ± 13.660.10− 0.37Diastolic blood pressure (mmHg)73.29 ± 6.8574.29 ± 8.920.62− 0.13Heart rate (beats/min)66.86 ± 9.1066.86 ± 7.10> 0.990.00Data are expressed as mean ± standard deviation
|
study
| 100.0 |
In the present pilot study, we examined whether handgrip exercise by the non-affected hand of a stroke patient promotes venous return in the contralateral, affected arm. We calculated venous flow volume according to the venous diameter and the time-averaged mean flow velocity in the axillary vein measured by US. We found that rhythmic resistance exercise by the non-affected hand significantly increased venous flow velocity and volume in the affected upper limb, although the diameter of the axillary vein showed no statistically significant increase. Additionally, a moderate effect was observed for a difference in both venous flow velocity and volume between the measurements at baseline and during resistance exercise. These new findings suggest that exercise by the non-affected hand promotes venous return in the contralateral, affected upper limb in hemiplegic patients.
|
study
| 100.0 |
This study is the first report of increased venous return due to exercise by the contralateral hand without any influence of the systemic circulation. As peripheral venous return is to the heart, it is recognized in two main factors: the muscle pump and the respiratory pump. In the present study, we speculated on the possibility of a third pump—a “contralateral limb exercise pump”—although the mechanism remains unclear. We suggest that it might be an effect of the pressure distribution of the superior vena cava during the exercise cycle.
|
study
| 100.0 |
There was no significant difference in the venous diameter between the baseline and resistance exercise conditions in this study, but the venous flow velocity significantly increased. In a previous study, Ojima et al. reported no differences in the popliteal vein or common femoral vein diameters between the at-rest condition and during electrical muscle stimulation, although peak venous flow velocities were higher during electrical muscle stimulation than at rest. Likewise, the increased venous flow volume resulted primarily from increases in the time-averaged mean flow velocity in this study using rhythmic handgrip exercise. Ishii et al. reported a heart rate increase during the early period (10–20 s) of voluntary one-arm cranking with 35–40% maximum voluntary contraction (MVC). Victor et al. reported that the mean arterial pressure and heart rate increased during the first minute of rhythmic handgrip at 30% MVC. However, there were no statistically significant differences in blood pressure or heart rate between the baseline and resistance exercise measurements in the present study because of the short exercise duration (20 s). Because of the differences in the exercise (including contraction and exercise times), the blood pressure and heart rate must not have been influenced in the present study. There were no adverse events attributable to the study conditions. We believe that the protocol used in the present study is safe.
|
study
| 99.94 |
Following stroke, hand edema on the affected side is a common complication. In previous studies, the effects of treatment for edema has had limited effectiveness, indicating that a novel treatment for edema of the affected hand would be required. In this pilot study, we clarified that venous return in the affected arm was promoted by handgrip exercising with the non-affected hand and that it was safe. Although using the affected arm for any activity is generally difficult for patients with hemiplegia, it is easy for them to move the non-affected hand. Hence, further research is necessary to confirm and expand upon the results of this study.
|
study
| 99.94 |
This preliminary study of seven male stroke patients found that resistance exercise by the non-affected hand increased venous flow velocity and volume in their contralateral, affected upper limb. The study included only a small number of subjects in supine position. Additional research is therefore encouraged to confirm the effectiveness of exercise by the non-affected hand to increase the venous return of the affected upper limb while in a sitting position or using a handgrip exercise without resistance.
|
study
| 99.94 |
The present study has some limitations. First, because it was a pilot study using a small sample, the results should be considered preliminary and viewed with caution, although resistance exercise induced a significant increase in venous flow velocity and volume compared with baseline. Second, resistance exercise was set at only 30% MVC of the handgrip. Ishii et al. suggested the possibility that one-armed passive arm motion causes a change in venous blood oxygenation and volume in non-contracting arm muscles. Therefore, the use of handgrip exercise without resistance should be established in a future study. Third, we measured the hemodynamics of the venous circulation in supine patients with stroke. It is generally recommended, however, that stroke patients be mobilized to an active sitting or standing position as soon after stroke as possible. Stern et al. reported that the venous volume of upper-extremity edema differs depending on the patient’s posture. Therefore, venous hemodynamics must be measured in stroke patients not only in the supine position but also when sitting.
|
study
| 99.94 |
Modern external beam radiotherapy features highly conformal, inversed‐planned treatment techniques such as IMRT and VMAT. However, even with these techniques, and factoring out variations in contouring, 1 , 2 , 3 , 4 the quality of treatment plans can vary greatly. Nelms et al. (5) reported a study where different institutions were asked to produce a plan based on the same downloadable CT dataset with presegmented targets and normal structures. Also provided was a clear set of planning goals given as a list of metrics and per‐metric scoring methodology, producing a cumulative score called the Plan Quality Metric (PQM). This approach eliminated two major sources of uncertainty for a plan quality study: (i) variability in anatomy and contouring, and (ii) variability and subjectivity in the measure of plan quality. In this well‐controlled study, the results showed substantial variation in plan quality. Moreover, the variation was not readily attributable to any common technical factors such as delivery technique or treatment planning system (TPS) used. The authors concluded the variation was generally due to differences in “planning skills”. Echoing these findings, the current state of treatment planning was summarized by Moore et al. (6) as “a very time‐consuming task with great output variability”.
|
review
| 99.9 |
One of the long‐established tenets in quality management—decreasing variability — is very much applicable to treatment planning, and is therefore one of the driving forces behind the development of more automated approaches. One proposed solution is based on the concept of machine learning. A database of previously accepted plans for a specific disease site is built. A new plan is supposed to achieve quality comparable to the previous cases with similar patient anatomy and objectives. 7 , 8 , 9 , 10 Another approach to partially automating the dose optimization process is implemented in the AutoPlanning (AP) software module, an option with Pinnacle v. 9.10 TPS (Philips Medical Systems, Fitchburg, WI). It requires no formal prior database of successful plans, but uses instead the iterative approach of progressive optimization. (11) The concept is largely to capture the steps that a skilled human operator would take and then mimic them for a new patient.
|
other
| 99.4 |
In this paper, we perform an initial evaluation of this autoplanning approach by measuring the quality of the AP‐produced plans and comparing them directly to the quality of traditional human‐driven clinical plans created for the same datasets. To facilitate quantitative analysis of overall plan quality, we applied the PQM approach. (5)
|
study
| 99.94 |
The job of the previously described Pinnacle optimizer (12) is to balance the competing objectives of target coverage and normal tissue sparing by minimizing the composite objective function. What is enhanced in AP is how the objectives are automatically created and used in iterative fashion. At the heart of the process is the concept called the “technique”. A technique includes a set of user‐supplied optimization goals, which follow the clinical dosimetry goals (Fig. 1). The target dose (left side of the figure) is defined by a single number (prescription dose). Additional user input is provided under Advanced Settings, where the maximum dose and a qualitative balance between target dose conformity and OAR sparing are set (Fig. 2). The Dose Fall‐Off Margin defines the width of an automatically created tuning ring structure around the PTV, across which the dose is supposed to decrease, ideally, from 100% to 50%. When Use Cold‐Spot ROIs box is checked, the AP engine identifies cold spots in the target and creates ROIs with corresponding objectives, to bring the dose up during the last three optimization loops.
|
study
| 99.8 |
The specific OAR goals are enumerated in the right panel. Their type could be Maximum or Mean dose, or a DVH point (volume at dose). As opposed to the weight factor from 0 to 100 used on the standard optimization tab, the user can qualitatively assign the relative importance of an individual goal (Priority) as High, Medium, or Low. It can be also specified as a hard constraint, but that option is seldom used as being too restrictive. The last column in Fig. 1 is Compromise. It is applicable to the situations when an OAR overlaps with a target. If the box is checked, it essentially means that the target owns the overlapping voxels and the OAR sparing could be compromised to achieve proper target coverage. That would be typically representative of a situation with a parallel OAR. For a serial OAR (e.g., the spinal cord), the box is left unchecked and the overlapping voxels are entirely owned by the OAR.
|
other
| 99.75 |
The software has an internal logic to check the level of overlap between a structure and a target and adjust the Priority accordingly. If a large portion of an OAR is inside the target volume and the Compromise box is checked, there is no point in having the priority set too high, and the software will automatically lower it according to the numerical level of overlap, based on 25% volume increments.
|
other
| 99.94 |
The core AP algorithm is based on the regional optimization concept introduced by Cotrutz and Xing, (13) but is implemented based on the ROIs, (11) as opposed to the original voxel‐based approach. It attempts to iteratively fine‐tune the target coverage and OAR sparing results by creating multiple additional structures, based both on the relative geometry of originally segmented regions of interest (ROI) and on the transient dose distributions transpiring during the optimization process. As those ROIs are created, they are automatically assigned dose‐volume objectives and added to the standard optimization tab, thus becoming an additional input to the optimizer. Those additional objectives are added to help meet high and medium priority goals.
|
other
| 98.8 |
This process of translating the clinical goals defined on the autoplanning page to the optimization objectives on the traditional IMRT tab (12) is fairly complex. The starting objectives are not visible to the user, only the final set, after the autoplanning process is complete. The exact rules of the ROIs' and corresponding objectives' creation are proprietary. However, some observations can be made from a relevant plan example.
|
other
| 99.9 |
A planning target volume (PTV) prescription goal of uniform 70 Gy was translated into the minimum and maximum dose objectives for the whole target of 70.7 (101%) and 71.05 (101.5%) Gy, respectively. In addition, partial PTV volumes, apparently considered underdosed after the initial iterations, were assigned a 70 Gy minimum dose objective.
|
other
| 98.75 |
When the maximum dose goal for the OAR is specified, it translates into the corresponding maximum dose objective(s). What can be discerned from comparing the goal and objectives tabs, is that for a single goal, the software can create more than one objective, with different values and weights. For example, for the spinal cord planning volume at risk (PRV) clinical goal of 45 Gy maximum dose, two maximum dose objectives were created for the final optimization: 42.75 Gy (relative weight 100%) and 19.51 Gy (low relative weight of 0.125%). On the other hand, in order to implement the maximum dose goal of 28 Gy to the oral cavity, the algorithm simply applied the 28 Gy maximum dose objective to the portion of the OAR outside the PTV. However, the weight was kept low (0.2%), presumably since the objective was clearly unachievable due to the immediate proximity of the oral cavity to the primary PTV.
|
other
| 73.06 |
For one goal for the parotid mean dose, two different maximum equivalent uniform dose (EUD) 14 , 15 objectives were applied to the derived ROI — the part of the OAR outside the PTV. In general, if the “biological optimization” option is enabled, AP would use the EUD objectives whenever the mean dose goals are specified.
|
other
| 99.75 |
The AP technique can be saved and recalled later. The set of goals in the technique is typically (but not necessarily) accompanied by a previously established beam arrangement class solution, which is automatically applied when the technique is recalled. The process of AP commissioning consists largely of designing, by trial and error, of the technique(s) that produce desired outcome for a class of cases with similar clinical goals. While theoretically not requiring prior knowledge, the technique evaluation process is clearly influenced by the operator's perceptions of what a good plan should look like, and by the prior experience with similar plans.
|
other
| 99.9 |
The plan quality scoring builds upon the previously established formalism (5) which is based on defining a collection of specific metrics (which can be DVH points, conformality indices, etc.) and corresponding score functions for each. Each metric's score function translates the achieved value to a numerical score. The sum over all metric scores divided by the combined maximum possible constitutes a composite PQM (%), used as a proxy for the overall achieved plan quality. The individual score functions are generally designed to define a failure region (where the score is zero), a transition region between the minimally acceptable and the ideal achievements (where the score increases from zero to the maximum), and the region exceeding the ideal (where the maximum score is awarded). Once the quality algorithm is defined, the analysis is automated and devoid of observer bias. However, it is important to understand that the metric scores inevitably carry a degree of subjectivity when used in aggregate, for a composite PQM. It is fundamentally unavoidable when attempting to quantify the relative importance of different clinical priorities. On the other hand, an individual metric score (rendered as percentage of the maximum possible) is used to compare only that specific achievement for the single ROI across the plans, and thus is devoid of “relative importance” subjectivity.
|
study
| 99.94 |
To perform a challenging test of the AP algorithm, we applied it to some of the most dosimetrically difficult cases encountered in our practice — locoregionally advanced head and neck cancers. Ten consecutive, previously treated cases were selected according to the following criteria: all were treated with 6 MV VMAT beams for 35 fractions, with 70 Gy to the primary target (PTV_70) and simultaneously 56 Gy to the elective bilateral neck nodes (PTV_56); all patients were under the care of the same radiation oncologist and planned by the same dosimetrist. All original plans employed two or three full VMAT arcs and were designed for a Varian linear accelerator with a 120‐leaf Millennium multileaf collimator (Varian Medical Systems, Palo Alto, CA). The physician manually drew the primary gross tumor volume (GTV) and the elective nodes clinical tumor volume (CTV). The GTV was expanded uniformly by 5 mm to create the 70 Gy CTV. This was manually edited to remove bone, fascia, and air. Both CTVs were expanded uniformly by 3 mm to arrive at the corresponding planning target volumes (PTV). The primary (PTV_70) average target volume was 338±262 (1 SD) cm3 with the range from 85 to 1035 cm3. The bilateral elective nodes (PTV_56) had the average volume of 352±94 cm3, with the range from 182 to 490 cm3.
|
study
| 100.0 |
Although the ultimate intention was to evaluate VMAT planning, we originally attempted to use fixed‐gantry IMRT with nine beams to develop the set of AP dosimetric goals, as IMRT takes far less planning time. However preliminary trials indicated that it was not feasible to achieve plans of acceptable quality by the institutional standards, which was consistent with our previous manual planning experience. Therefore the AP techniques were developed with VMAT. To minimize the influence of delivery mechanical constraints on plan quality, all AP plans involved three full arcs with maximum delivery time of 140 s per beam and MLC motion constrained to 0.46 cm per 1° of gantry rotation. (16) Allowing this ample delivery time during optimization provides the necessary freedom to the optimization algorithm, while the linac software usually finds a faster way to deliver the resulting plan. (16) Full convolution calculation was performed after the 10th optimization iteration and the total number of iterations was limited to 100. The collimator was typically rotated ±15∘, except when a different angle was dictated by the target size. All plans were calculated on a 3×3×3 mm3 grid with the Adaptive version of Pinnacle Collapsed Cone Convolution algorithm. (17) Following the recommendations by Yartsev et al. (18) for planning studies, the starting technique is presented in full detail in Table 1. This technique was used for the first series of autoplans (AP1) and was developed with vendor's assistance. The advanced tuning settings used for all APs are shown in Fig. 2.
|
study
| 100.0 |
Note that PTV_70 appears in this example twice (once as is, and once expanded by 1 mm to differentiate from the original). Initial experimentation has determined that one of the main AP challenges was to achieve adequate target coverage. Repeating the objective is just a practical way of instructing the optimizer to treat the target coverage with additional priority.
|
other
| 99.9 |
The remaining techniques (APs 2‐5) were slight variations of the first one. The changes were primarily limited to attempts to improve target coverage and dose homogeneity. Since we require the entirety of the GTV to be covered by the prescription isodose, AP 2 and 3 included GTV as a separate target, with slightly higher dose goals. If GTV coverage were to improve, that would help to avoid excessive renormalization and thus improve dose homogeneity. In AP 4, a repeating goal was added for the secondary PTV (PTV_56 + 1 mm) in an attempt to achieve better coverage of the secondary target. For AP 5, in addition to having the GTV goals, two new tuning structures were created around the PTVs. The first one was a 1 cm expansion of PTV_70 and it was assigned a high priority maximum dose goal of 73.5 Gy. The second one was a part of PTV_56 at least 1 cm away from PTV_70. It was assigned a high priority maximum dose goal of 60 Gy. In the same technique, an additional larynx goal was introduced (maximum DVH dose of 35 Gy to 75% of the volume). All five techniques were applied to each of 10 cases, resulting in 50 autoplans.
|
study
| 99.94 |
A basic goal of the evaluation is to determine if an automated planning routine can consistently and reliably produce “clinically acceptable” plans, which would define its success or failure in practice. It is important to note that “acceptable” (i.e., meeting minimal constraints) does not necessarily imply a plan of highest possible quality. The definition of acceptable is somewhat subjective and may vary from institution to institution and physician to physician. Therefore, we felt that it would be unfair to label the AP plans acceptable or unacceptable based on our internal criteria. Instead, for the initial screening, we adopted the consensus‐driven approach, from the RTOG protocol No. 1016. (19) This particular H&N protocol uses the same primary and secondary dose levels (70 and 56 Gy) and has six dosimetric criteria that determine plan acceptability (Table 2). Of those six criteria, five deal with the target dose level and homogeneity, and one is concerned with the maximum dose to the spinal cord. The rest of the OAR sparing objectives are on the “best effort” basis, although recommendations on dose levels and priorities are provided.
|
study
| 99.94 |
There are slight differences with the protocol in how we apply the acceptability criteria. For the protocol, the first line in the table is automatically fulfilled if the plan is normalized as specified. We normalize out plans to cover 100% of the GTV with 100% of the prescription dose. Although this approach typically produces sufficient PTV coverage, compliance with the protocol had to be tested. The 0.03 cm3 cold spot was first evaluated for the entire PTV_70. If failed, it was examined for the lesser volume as specified in the protocol, namely disregarding the PTV voxels residing closer than 8 mm from the skin.
|
other
| 81.1 |
The individual metric score functions used to calculate the plan quality scores are presented in Table 3, on the left. The minimum number of points necessary to describe every function is given. A step function is thus defined by one value/score combination, a single‐slope linear function by two, and two linear segments with different slopes by three. Examples of how the value/score pairs from Table 3 define the shape of the score function for each of the three scenarios above are given in Fig. 3.
|
study
| 99.9 |
The score functions reflected the target and OAR goals routinely employed in our clinic and recorded on the formalized objective sheets. They were defined prior to commencement of the AP evaluation. The OAR score values are based on biological endpoints 20 , 21 , 22 , 23 and attempt to capture the physician's perception of the relative importance of different dose goals. Taking the parotid gland as an example, the maximum available score is 15, relative to the target coverage maximum score of 25. This reflects the facts that curing cancer is considered more important than preserving salivary function and that the parotids are not the only saliva‐producing glands. The parotid dose/score points are based on the simplified version of the normal tissue complicated probability (NTCP) curve from Dijkema et al. (23) who plotted the probability of saliva flow ratio at 1 year reduced to <25% against the mean parotid dose. As seen in Table 3, 15 points is awarded for the mean dose of 15 Gy (∼5% NTCP), 10 points for 26 Gy (∼25% NTCP), and 5 points for 39 Gy (≤50 NTCP). No points are awarded above 39 Gy. Thus the AP5 average mean parotid dose PQM score in Table 3 (74.8%) is equivalent to 0.748×15=11.2 points. From the plot in Fig. 3, it translates back into the absolute dose of 23.7 Gy. Similar calculations can be easily performed, if desired, for every objective in Table 3.
|
study
| 100.0 |
Table 3 is divided into four parts. The first three list the objectives that were used for planning and evaluation, grouped into Target Coverage, Target Dose Homogeneity, and OAR Sparing categories. The last group of indices, Excluded From Scoring, contains two entries that were not a part of the original plan evaluation and comparison, but were deemed worthwhile to investigate after the fact. Total irradiated volume at 73.5 Gy (105% of prescription) is self‐explanatory. The Conformation Number (CN) (24) is one of several ways (25) to quantify the reference isodose volume (70 Gy) conformality to the target (PTV_70). It is defined as (1)CN=VT,refVT×VT,refVref where VT,ref is the volume of target receiving a dose equal to or greater than the reference dose, VT is the target volume, and Vref is the volume receiving a dose equal to or greater than the reference dose.
|
study
| 99.9 |
For each patient, the overall PQM score was recorded for the original plan and the test plans generated from five different AP templates for this study. This means that overall 60 plans were generated and analyzed. An AP template with the highest average composite score across 10 patients was selected as the best one, and the plans it produced were compared to the original human‐driven plans (HDPs) in greater detail, at the individual goals level.
|
study
| 99.94 |
Since, following the PQM method, all results were recorded as a percentage of the predefined maximum possible score (whether combined or for individual objectives), a higher number always means a more desirable result, whether the context is covering or sparing. The only exception is the last two lines in Table 3, which contain absolute values. Not every OAR was segmented and evaluated for every plan (see the last column in Table 3 showing in parenthesis the number of cases where each objective was scored). However since for each patient the same set of OARs was evaluated, the cumulative score comparison between the different plans for the same case is still valid.
|
study
| 100.0 |
The left half of the table lists all the planning and evaluation objectives: the ROI, the type of objective (dose to volume, volume at dose or other), and the goal values with associated scores (e.g., the score functions). The right half presents the resulting descriptive statistics comparing the human‐driven plan (HDP) and the overall highest‐scoring PQM autoplan (AP 5). The last column lists the p‐value for the Wilcoxon test (number of pairs).
|
other
| 99.44 |
The goal was to ascertain if there was a statistically significant difference between the scores for the HDPs and APs aggregated across the patient population. Both total and individual objectives' scores were compared. The nonparametric Wilcoxon matched‐pairs, signed‐rank test was used with p‐value below 0.05 considered significant. This test is used to determine if the medians of two paired distributions are statistically different when the distributions cannot be assumed Gaussian. The analysis was implemented in GraphPad Prism v. 6.0 software (GraphPad Software, La Jolla, CA).
|
study
| 99.94 |
For both HDPs and APs, 95% percent of both PTV_70 and PTV_56 volumes were covered by the respective prescription doses with no deviations. Likewise, the cord constraint was always fulfilled. With the rest of the acceptability criteria, for nine out of ten patients, all plans either fully complied with the protocol or exhibited only minor deviations. With one patient, no plan was able to keep the 0.03 cc cold spot above 63 Gy for the original PTV_70 and only the HDP achieved a minor deviation with PTV_70 cropped 8 mm away from the skin (64.8 Gy). The AP PTV_70 cold spots ranged from 59.7 to 62.1 Gy. For all other patients, the cold spot was RTOG‐acceptable, even with the full PTV_70.
|
study
| 98.8 |
The descriptive statistics of the composite PQM are presented in Table 4 for the HDPs and five APs. The technique modification efforts described in Methods had some desired effects. In AP4, adding the second, nearly identical PTV_56 objective increased the number of cases where the dose to 100% of PTV_56 was at or above 53.2 Gy from 3 to 7 out of 10. It is the same number as for the HDP (although not in all the same cases). The plans generated by technique No. 5 (AP 5) had the highest average PQM among the APs and that technique was selected for detailed evaluation. This improvement in the AP composite score is attributable to the success of additional operator‐added tuning structures in improving dose homogeneity. Combining the scores for the goals of maximum dose and PTV_70 volume at or above 73.5 Gy, the average for AP 5 stands at 47.2%, with the next best one, AP 2, at 35.4%. For comparison, the HDP achieved 91.1% on average.
|
study
| 100.0 |
The median composite PQM scores are statistically different between the HDPs (65.4%±10.9% (1 SD), and AP 5 plans (59.9%±9.1%). Wilcoxon test p‐value for median difference was 0.027. Note that the relatively low reported scores are indicative not of the poor quality plans but rather of the high evaluation bar. For example, to score 100%, the mean parotid dose must be no more than 15 Gy, as opposed to the RTOG 1016 26 Gy guideline. (19) The detailed comparison at the individual objectives level is presented in Table 3, on the right‐hand side.
|
study
| 100.0 |
In terms of target coverage, as described above, every plan delivered at least 70 Gy to 95% of the PTV_70 volume. Similarly, 95% of PTV_56 volume was always covered by the 56 Gy isodose. The minimum PTV dose was below desired 66.5 Gy (95% of prescription) in the same three cases for both the APs and the HDPs. This does not contradict the previously described analysis by the RTOG 1016 criteria, since the minimum dose here is defined for a single voxel. Finally, there was a difference, albeit not statistically significant, in the minimum dose (single voxel) to PTV_56. Three HDPs and seven APs failed to reach the 53.2 Gy (95% of prescription) goal. However, for one patient the HDP failed and the AP did not.
|
study
| 100.0 |
Although adding a tuning structure (in AP 5) has improved dose homogeneity some, the AP results in this subgroup are still inferior to the HDPs. The maximum dose (single voxel) was lower with high statistical significance (p=0.008) for the HDPs. For those, only one case had a hot spot above 107% of prescription (0 score), and six cases recorded ≤105 of prescription (100% score). At the same time, six of the APs failed to maintain the maximum dose below 107% of the prescription, and only one had the hot spot under 105%. Also statistically significant (p=0.03) was the difference for the PTV volume at or above 73.5 Gy (105% of prescription). In all HDPs, the volume did not exceed 1 cm3 (100% score). Four of the APs achieved the same result, while one had the ≥105% dose volume in the PTV above 15 cm3 (zero score), with the remaining five falling in between 1 and 15 cm3. While not a part of the tabulated composite score, the total volume irradiated to at least 73.5 Gy exhibited highly statistically significant difference between the median values of the HDPs and APs (p=0.004). In the HDPs, it was kept consistently low (0−3.9 cm3), while for the APs it varied widely from 1 to 501.8 cm3. Once again, this does not contradict the RTOG 1016 acceptability analysis since the hot spot here is defined more stringently: at a lower level (75 vs. 82 Gy) and for a single voxel, as compared to 1 cm3 in the protocol. For the HDPs, the hot spot was always located either in the GTV (3 cases) or PTV_70. For the APs, the hot spot was located in PTV_70 eight times, and twice elsewhere. Interestingly, despite the difference in dose homogeneity, the conformity number between PTV_70 and the 70 Gy dose volume was essentially the same between the HDPs and APs.
|
study
| 100.0 |
While the dose homogeneity scores favor the HDPs over the APs, the trend is largely reversed for OAR sparing. Both the cord and the brain stem maximum dose (single voxel) PQM scores are statistically significantly higher (meaning lower dose) for the APs (Table 3). The parotid mean dose score is also higher for the APs with high statistical significance (p<0.001). The last OAR with a statistically significant advantage for the APs was the inferior pharyngeal constrictor.
|
study
| 100.0 |
To facilitate a more familiar mode of the data review, the parameters found to have statistically significant differences between the HDPs and APs are recast in Table 5 in terms of original dose‐volume points, as opposed to the normalized scores in Table 3. In addition, the DVH curves for those structures, along with the targets, are presented in Fig. 4 for all 10 cases. It is immediately clear that, when the goal is to minimize the mean (EUD) OAR dose (the parotids and IPC), the corresponding AP DVH curves run consistently below the HDP ones. On the other hand, when only the maximum dose goal is specified (the cord and brainstem), the relative shape of the DVH curves varies.
|
review
| 99.6 |
The difference between the HDP and AP scores did not achieve statistical significance for the remaining 26 normal tissue sparing objectives. Of those, 24 scores were equally divided in being either equal or higher for the APs, and two were in favor of the HDPs (percentages of larynx volume at or above 45 and 55 Gy). However the scores for the mean larynx dose and the volume at or above 35 Gy were higher for the APs. Incidentally, those were the two parameters that showed improvement after modifying the larynx goal in AP5.
|
study
| 100.0 |
Representative dose‐volume histograms for all cases. Solid lines represent HDP and dashed AP 5. Structure names are color‐coded on the graphs (PTV 70 and 56 Gy, Left and Right Parotids, Cord+5 mm, Brainstem+5 mm, and Inferior Pharyngeal Constrictor (IPC)).
|
other
| 99.44 |
To deliver a desired dose to the target, a certain amount of radiative energy has to cross its surface, depending on the size. That energy fluence cannot be reduced. What can be influenced is the pattern in which this energy is delivered. The process of treatment planning attempts to find a pattern that strikes a reasonable compromise between the three competing priorities: target coverage, target dose homogeneity, and sparing of the adjacent OARs. A TPS optimizer is essentially a black box to the user. A set of numbers (objectives) is provided as an input, resulting in an output (a dose distribution typically further reduced to a set of DVHs). Ideally, the inputs should be intuitive, and the black box should be sensitive and linear (e.g., allow for an easy shift in the priorities and direct proportionality between the change in the input and corresponding output).
|
other
| 99.9 |
The input parameters to Pinnacle AP are rather intuitive. They are for the most part clinical dose‐volume goals, with a few “tricks of the trade” applied occasionally (see AP technique development strategy section in Methods). However, what we found in this work is that the AP algorithm seems to have a natural tendency to favor OAR sparing over target coverage and closely related target dose homogeneity. The higher composite PQM scores for the human‐driven plans are a reflection of the institutional priorities for the H&N plans built into the scoring algorithm, as we put a premium on target dose homogeneity. Other institutions or physicians may be willing to accept larger hot spots in exchange for better OAR sparing. If one is satisfied with meeting the basic RTOG 1016 hot and cold spot criteria, the AP OAR sparing results are actually preferable. What AP is apparently lacking, at least at our level of experience, is an easy tool to move the balance between dose homogeneity and OAR sparing. While problematic with our approach to the conventional H&N planning, the relative ease of achieving a lower dose to the OARs at the expense of higher hot spots could be beneficial, for example, for radiosurgery‐type treatments, where the target dose inhomogeneity is mandated rather than discouraged. (26)
|
study
| 99.94 |
Perhaps the most intriguing feature of the Pinnacle autoplanning engine is that it is designed, according to the vendor, to push the dosimetric indices beyond the specified goals and towards achievable limits. To definitively verify this claim, one needs to formally demonstrate that the resulting plans are Pareto‐optimal (i.e., no objective can be improved upon without simultaneously sacrificing at least one other). (27) This task is formidable (28) even with the proposed reduction in the number of evaluated plans, 29 , 30 and typically five or fewer dose objectives were considered in the cited references. Therefore Pareto analysis, particularly exhaustive in terms of the structures, was beyond the scope of the current practical study. However, using a composite plan quality metric encompassing challenging evaluation scores is a step in the right direction. Applying it to select the best technique helps to find a balanced solution, where a dosimetric improvement for one structure is more likely to result in deterioration for the other(s). Furthermore, achieved dose values for certain OARs were routinely below the specified goals. This is consistent with the claimed algorithm behavior, although does not prove it. Further studies, with different methodology, are needed to find out if the dose homogeneity could be improved without sacrificing OAR sparing.
|
study
| 100.0 |
A novel automated treatment planning algorithm was evaluated on 10 realistic, challenging VMAT head and neck cases in comparison with the traditional human‐driven plans used for actual treatments. Side‐by‐side comparisons were performed using objective, formalized plan quality metrics. Human‐driven plans provided more homogeneous dose distributions and the autoplans excelled at limiting the OAR doses, while still conforming to the relevant RTOG dose homogeneity requirements. The DVHs for some OARs were driven by AutoPlanning beyond the specified goals, but overall this study was not equipped to probe if the software produced Pareto‐optimal plans. AutoPlanning appears to be a robust clinical tool, but it would be, in our opinion, beneficial to improve the user controls for rebalancing the optimization compromise away from OAR sparing and towards dose homogeneity, to better fit the range of preferences of different clinicians.
|
study
| 100.0 |
Drought, climate change and pollution subject our water resources to big changes, and as the situation gets worse with time, more people experience its negative effects; currently, four out of every 10 people in the world are affected by a lack of water. Our population continues to grow and with it our needs for more water grow, for both industrial and domestic purposes. Our work focuses on optimizing water management in the agricultural sector, being the largest economic sector in the world. It is estimated that the agricultural industry wastes 60% of the 2.500 billion litres of water used each year . In comparison to the current crop irrigation systems, we seek a more economic and effective solution that incorporates intelligence and context-awareness. This is possible due to the remarkable progress that has been made in the field of electronics in the last decade, whereby the size of end devices has decreased and their production costs as well. As a result, a variety of low cost sensors and communication devices is now available, allowing us to propose new solutions that can solve many every day challenges in an economic way. The possibility of using sensor networks in the agricultural sector would allow us to acquire data and look for intelligent solutions, helping us to create a system that ensures proper crop growth and optimizes water usage. However, the current monitoring systems do not incorporate a minimum degree of intelligence and do not have the ability to adapt to the environment. Moreover, the implementation of industrial equipment for the control of crop irrigation is hindered by its high cost and complexity; the lack of such equipment on farms results in unnecessary water wastage.
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other
| 99.56 |
A multi-agent system (MAS) is the most suitable option for this solution. This is because a MAS includes an Intelligent Distributed Artificial System, which incorporates social aspects and human reasoning to solve problems. Specifically, this work proposes an architecture based on virtual organizations through the use of a multi-agent open source platform called PANGEA , which incorporates services that allow sensor networks to be interconnected. This design makes it possible for agent societies to include organizational aspects of human societies, improving self-regulation and self-organization. The use of autonomous agents embedded in devices with limited computing capabilities makes the PANGEA platform a perfect candidate for the planned system. Each agent may represent an autonomous entity that consumes and provides different services. Collaboration between agents from the same organization offers more distributed and complex functionalities. One of the challenges that must be faced in this work is the fusion of information that comes from heterogeneous sources; the aim is to design an agent type that fuses heterogeneous data and obtains the crops’ growth patterns. The proposed system should guarantee growth and scalability of the platform.
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other
| 99.56 |
The assignment of roles to virtual organizations of agents will ensure system flexibility and will provide us with the ability to add new functionalities, creating a completely transparent layer for the applications that are developed for the user. The communication between the different components of the system must be efficient and low power consuming, since it must be capable of operating without direct sunlight. The proposed system must be able to monitor a crop and automatically supply the amount of water needed, this will be done through a predictive model with input variables regarding the climate, humidity of the subsoil, the force of wind, sunlight, temperature and the time of the day. Fields generally have very vast areas of land and sensors often have to be installed at large distances from one another, this is why a wireless connection between them is necessary. To this end, a network of autonomous sensors has been designed, with manageable battery consumption, which coordinates and generates different events produced in the system. Wireless Sensor Networks (WSNs) are used to analyse environmental behaviour and the existing interaction between different sensors, they make decisions automatically on a daily basis .
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other
| 99.9 |
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