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1.  A Pilot Prospective Feasibility Study of Organ-at-Risk Definition using Target Contour Testing/Instructional Computer Software (TaCTICS), a Training and Evaluation Platform for Radiotherapy Target Delineation. 
Target volume delineation is a critical, but time-consuming step in the creation of radiation therapy plans used in the treatment of many types of cancer. However, variability in target volume definitions can introduce substantial differences in resulting doses to tumors and critical structures. We developed TaCTICS, a web-based educational training software application targeted towards non-expert users. We report on a small, prospective study to evaluate the utility of this online tool in improving conformance of regions-of-interest (ROIs) with a reference set. Eight residents contoured a set of structures for a head-and-neck cancer case. Subsequently, they were provided access to TaCTICS as well as contouring atlases to allow evaluation of their contours in reference to other users as well as reference ROIs. The residents then contoured a second case using these resources. Volume overlap metrics between the users showed a substantial improvement following the intervention. Additionally, 66% of users reported that they found TaCTICS to be a useful educational tool and all participants reported they would like to use TaCTICS to track their contouring skills over the course of their residency.
PMCID: PMC3243186  PMID: 22195121
2.  Freehand Liver Volumetry by Using an Electromagnetic Pen Tablet: Accuracy, Precision, and Rapidity 
Journal of Digital Imaging  2010;24(2):360-365.
The purpose of this study is to assess the accuracy, precision, and rapidity of liver volumes calculated by using a freehand electromagnetic pen tablet contourtracing method as compared with the volumes calculated by using the standard optical mouse contourtracing method. The imaging data used as input for accuracy and precision testing were computed by software developed in our institution. This computer software can generate models of solid organs and allows both standard mouse-based and electromagnetic pen-driven segmentation (number of data sets, n = 70). The images used as input for rapidity testing was partly computed by modeling software (n = 70) and partly selected from contrast-enhanced computed tomography (CT) examinations (n = 12). Mean volumes and time required to perform the segmentation, along with standard deviation and range values with both techniques, were calculated. Student's t test was used to assess significance regarding mean volumes and time calculated by using both segmentation techniques on phantom and CT data sets. P value was also calculated. The mean volume difference was significantly lower with the use of the freehand electromagnetic pen as compared with the optical mouse (0.2% vs. 1.8%; P < .001). The mean segmentation time per patient was significantly shorter with the use of the freehand electromagnetic pen contourtracing method (354.5 vs. 499.1 s on phantoms; 457.4 vs. 610.0 s on CT images; P < .001). Freehand electromagnetic pen-based volumetric technique represents a technologic advancement over manual mouse-based contourtracing because of the superior statistical accuracy and sensibly shorter time required. Further studies focused on intra- and interobserver variability of the technique need to be performed before its introduction in clinical application.
PMCID: PMC3056975  PMID: 20352280
Liver volumetry; computed tomography (CT); pen tablet; contour tracing
3.  Tablet Keyboard Configuration Affects Performance, Discomfort and Task Difficulty for Thumb Typing in a Two-Handed Grip 
PLoS ONE  2013;8(6):e67525.
When holding a tablet computer with two hands, the touch keyboard configuration imposes postural constraints on the user because of the need to simultaneously hold the device and type with the thumbs. Designers have provided users with several possible keyboard configurations (device orientation, keyboard layout and location). However, potential differences in performance, usability and postures among these configurations have not been explored. We hypothesize that (1) the narrower standard keyboard layout in the portrait orientation leads to lower self-reported discomfort and less reach than the landscape orientation; (2) a split keyboard layout results in better overall outcomes compared to the standard layout; and (3) the conventional bottom keyboard location leads to the best outcomes overall compared to other locations. A repeated measures laboratory experiment of 12 tablet owners measured typing speed, discomfort, task difficulty, and thumb/wrist joint postures using an active marker system during typing tasks for different combinations of device orientation (portrait and landscape), keyboard layout (standard and split), and keyboard location (bottom, middle, top). The narrower standard keyboard with the device in the portrait orientation was associated with less discomfort (least squares mean (and S.E.) 2.9±0.6) than the landscape orientation (4.5±0.7). Additionally, the split keyboard decreased the amount of reaching required by the thumb in the landscape orientation as defined by a reduced range of motion and less MCP extension, which may have led to reduced discomfort (2.7±0.6) compared to the standard layout (4.5±0.7). However, typing speed was greater for the standard layout (127±5 char./min.) compared to the split layout (113±4 char./min.) regardless of device orientation and keyboard location. Usage guidelines and designers can incorporate these findings to optimize keyboard design parameters and form factors that promote user performance and usability for thumb interaction.
PMCID: PMC3694062  PMID: 23840730
4.  Improved operator agreement and efficiency using the minimum area contour change method for delineation of hyperintense multiple sclerosis lesions on FLAIR MRI 
BMC Medical Imaging  2013;13:29.
Activity of disease in patients with multiple sclerosis (MS) is monitored by detecting and delineating hyper-intense lesions on MRI scans. The Minimum Area Contour Change (MACC) algorithm has been created with two main goals: a) to improve inter-operator agreement on outlining regions of interest (ROIs) and b) to automatically propagate longitudinal ROIs from the baseline scan to a follow-up scan.
The MACC algorithm first identifies an outer bound for the solution path, forms a high number of iso-contour curves based on equally spaced contour values, and then selects the best contour value to outline the lesion. The MACC software was tested on a set of 17 FLAIR MRI images evaluated by a pair of human experts and a longitudinal dataset of 12 pairs of T2-weighted Fluid Attenuated Inversion Recovery (FLAIR) images that had lesion analysis ROIs drawn by a single expert operator.
In the tests where two human experts evaluated the same MRI images, the MACC program demonstrated that it could markedly reduce inter-operator outline error. In the longitudinal part of the study, the MACC program created ROIs on follow-up scans that were in close agreement to the original expert’s ROIs. Finally, in a post-hoc analysis of 424 follow-up scans 91% of propagated MACC were accepted by an expert and only 9% of the final accepted ROIS had to be created or edited by the expert.
When used with an expert operator's verification of automatically created ROIs, MACC can be used to improve inter- operator agreement and decrease analysis time, which should improve data collected and analyzed in multicenter clinical trials.
PMCID: PMC3766707  PMID: 24004511
Multiple sclerosis; Detection error; Outline error; Rater agreement; Operator agreement; Metric; Jaccard index; Similarity index; Kappa; Lesion; Assessment; Minimum area contour change
5.  Accuracy of deformable image registration for contour propagation in adaptive lung radiotherapy 
Deformable image registration (DIR) is an attractive method for automatic propagation of regions of interest (ROIs) in adaptive lung radiotherapy. This study investigates DIR for automatic contour propagation in adaptive Non Small Cell Lung Carcinoma patients.
Pre and mid-treatment fan beam 4D-kVCT scans were taken for 17 NSCLC patients. Gross tumour volumes (GTV), nodal-GTVs, lungs, esophagus and spinal cord were delineated on all kVCT scans. ROIs were propagated from pre- to mid-treatment images using three DIR algorithms. DIR-propagated ROIs were compared with physician-drawn ROIs on the mid-treatment scan using the Dice score and the mean slicewise Hausdorff distance to agreement (MSHD). A physician scored the DIR-propagated ROIs based on clinical utility.
Good agreement between the DIR-propagated and physician drawn ROIs was observed for the lungs and spinal cord. Agreement was not as good for the nodal-GTVs and esophagus, due to poor soft-tissue contrast surrounding these structures. 96% of OARs and 85% of target volumes were scored as requiring no or minor adjustments.
DIR has been shown to be a clinically useful method for automatic contour propagation in adaptive radiotherapy however thorough assessment of propagated ROIs by the treating physician is recommended.
PMCID: PMC3816595  PMID: 24139327
Deformable image registration; Adaptive radiotherapy; NSCLC; Automatic contour propagation
6.  Alternative User Interface Devices for Improved Navigation of CT Datasets 
Journal of Digital Imaging  2009;24(1):126-134.
The workflow in radiology departments has changed dramatically with the transition to digital PACS, especially with the shift from tile mode to stack mode display of volumetric images. With the increasing number of images in routinely captured datasets, the standard user interface devices (UIDs) become inadequate. One basic approach to improve the navigation of the stack mode datasets is to take advantage of alternative UIDs developed for other domains, such as the computer game industry. We evaluated three UIDs both in clinical practice and in a task-based experiment. After using the devices in the daily image interpretation work, the readers reported that both of the tested alternative UIDs were better in terms of ergonomics compared to the standard mouse and that both alternatives were more efficient when reviewing large CT datasets. In the task-based experiment, one of the tested devices was faster than the standard mouse, while the other alternative was not significantly faster. One of the tested alternative devices showed a larger number of traversed images during the task. The results indicate that alternative user interface devices can improve the navigation of stack mode datasets and that radiologists should consider the potential benefits of alternatives to the standard mouse.
PMCID: PMC3046793  PMID: 19949832
Navigation; user interface; PACS; computed tomography
7.  Cue dependent right hemineglect in schizophrenia: a kinematic analysis 
OBJECTIVES—Schizophrenia may result from disturbed attentional processes and/or defective internal cueing. Attention for subsequent action within a cued movement task was therefore studied, testing specific hypotheses of hemispheric dysfunction and of impaired interhemispheric communication.
METHOD—Fifteen patients with schizophrenia and 15 matched controls were either cued or uncued when moving a pen to a target on their right or left side with their right or left hand. Pen tip position was sampled at 200 Hz on a WACOM SD420 graphics tablet for subsequent kinematic analysis.
RESULTS—Patients with schizophrenia were slower initiating rightwards movements without a cue. Patients also exhibited reduced abductive/adductive differences in the shape of their movement trajectories, implying differences in interhemispheric communication.
CONCLUSIONS—It is speculated that schizophrenia is a form of cue dependent right hemineglect.

PMCID: PMC2170310  PMID: 9771765
8.  A Low-Cost, Computer-Interfaced Drawing Pad for fMRI Studies of Dysgraphia and Dyslexia 
Sensors (Basel, Switzerland)  2013;13(4):5099-5108.
We have developed a pen and writing tablet for use by subjects during fMRI scanning. The pen consists of two jacketed, multi-mode optical fibers routed to the tip of a hollowed-out ball-point pen. The pen has been further modified by addition of a plastic plate to maintain a perpendicular pen-tablet orientation. The tablet is simply a non-metallic frame holding a paper print of continuously varying color gradients. The optical fibers are routed out of the MRI bore to a light-tight box in an adjacent control room. Within the box, light from a high intensity LED is coupled into one of the fibers, while the other fiber abuts a color sensor. Light from the LED exits the pen tip, illuminating a small spot on the tablet, and the resulting reflected light is routed to the color sensor. Given a lookup table of position for each color on the tablet, the coordinates of the pen on the tablet may be displayed and digitized in real-time. While simple and inexpensive, the system achieves sufficient resolution to grade writing tasks testing dysgraphic and dyslexic phenomena.
PMCID: PMC3673127  PMID: 23595203
fMRI; MRI-compatible; dygraphia; dyslexia; lexical; handwriting; LabVIEW
9.  Using a reference tissue model with spatial constraint to quantify [11C]Pittsburgh compound B PET for early diagnosis of Alzheimer’s disease 
NeuroImage  2007;36(2):298-312.
Reference tissue model (RTM) is a compartmental modeling approach that uses reference tissue time activity curve (TAC) as input for quantification of ligand-receptor dynamic PET without blood sampling. There are limitations in applying the RTM for kinetic analysis of PET studies using [11C]Pittsburgh compound B ([11C]PIB). For region of interest (ROI) based kinetic modeling, the low specific binding of [11C]PIB in a target ROI can result in a high linear relationship between the output and input. This condition may result in amplification of errors in estimates using RTM. For pixel-wise quantification, due to the high noise level of pixel kinetics, the parametric images generated by RTM with conventional linear or nonlinear regression may be too noisy for use in clinical studies.
We applied RTM with parameter coupling and a simultaneous fitting method as a spatial constraint for ROI kinetic analysis. Three RTMs with parameter coupling were derived from a classical compartment model with plasma input: a RTM of 4 parameters (R1, k′2R, k4, BP) (RTM4P); a RTM of 5 parameters (R1, k2R, NS, k6, BP) (RTM5P); and a simplified RTM (SRTM) of 3 parameters (R1, k′2R, BP) (RTM3P). The parameter sets [k′2R, k4], [k2R, NS, k6], and k′2R are coupled among ROIs for RTM4P, RTM5P, and RTM3P, respectively. A linear regression with spatial constraint (LRSC) algorithm was applied to the SRTM for parametric imaging. Logan plots were used to estimate the distribution volume ratio (DVR) (= 1 + BP (binding potential)) in ROI and pixel levels. Ninety-minute [11C]PIB dynamic PET was performed in 28 controls and 6 individuals with mild cognitive impairment (MCI) on a GE Advance scanner. ROIs of cerebellum (reference tissue) and 15 other regions were defined on coregistered MRI’s.
The coefficients of variation of DVR estimates from RTM3P obtained by the simultaneous fitting method were lower by 77 - 89% (in striatum, frontal, occipital, parietal, and cingulate cortex) as compared to that by conventional single ROI TAC fitting method. There were no significant differences in both TAC fitting and DVR estimates between the RTM3P and the RTM4P or RTM5P. The DVR in striatum, lateral temporal, frontal and cingulate cortex for MCI group was 25% to 38% higher compared to the control group (p ≤ 0.05), even in this group of individuals with generally low PIB retention. The DVR images generated by the SRTM with LRSC algorithm had high linear correlations with those from the Logan plot (R2 = 0.99). In conclusion, the RTM3P with simultaneous fitting method is shown to be a robust compartmental modeling approach that may be useful in [11C]PIB PET studies to detect early markers of Alzheimer’s disease where specific ROIs have been hypothesized. In addition, the SRTM with LRSC algorithm may be useful in generating R1 and DVR images for pixel-wise quantification of [11C]PIB dynamic PET.
PMCID: PMC2001263  PMID: 17449282
10.  Comparison of the Dose Accuracy of Prefilled Insulin Pens 
Prefilled insulin pens have become a convenient and accurate way for diabetes patients to inject insulin. Their ease of use has helped to reduce the resistance of patients with type 1 diabetes and type 2 diabetes in the United States and Europe toward initiation of insulin therapy. This study compared the dosing accuracy of two prefilled insulin pens (the SoloStar® from Sanofi Aventis, Berlin, Germany, and the Next Generation [NG] FlexPen® from Novo Nordisk, Mainz, Germany).
The dosing accuracy was tested for both pens with × 24 10 international units of insulin (IU) and 9 × 30 IU injection volumes to investigate whether the pens comply within the acceptable International Organization for Standardization (ISO) limits of 10% (±1 IU) for 10 IU and 5% (±1.5 IU) for 30 IU. The doses were applied each with a new needle strictly according to the instructions for use of the pen manufacturers. A sensitive pharmaceutical balance was used for the assessment of the applied volumes, and the results were corrected for the specific density of the insulin formulations. We used 18 insulin pens (from two different production lots each) for the two volumes, respectively, resulting in a total of 432 doses per pen with 10 IU and 162 doses per pen with 30 IU.
Both pens showed a very good performance, which was better for the 10 IU dose than in comparative previous studies. The NG FlexPen (mean absolute percent deviation 10 IU/30 IU: 1.63 ± 0.84%/1.23 ± 0.76%) was even more accurate than the SoloStar (2.11 ± 0.92%/1.54 ± 0.84%, p < .001/p < .05 versus the NG FlexPen). Only 0.2% of the doses were outside the ISO limit at 10 IU, with the NG FlexPen (0.6% at 30 IU). The corresponding figures for the SoloStar were 0.4% and 1.8%, respectively.
A direct head-to-head comparison of the two prefilled insulin pens with a standardized protocol resulted in a more stable dosing accuracy of both pens as compared to previous investigations. In this investigation, the NG FlexPen was more accurate than the SoloStar at both tested doses.
PMCID: PMC2769835  PMID: 20046658
accuracy; disposable pen; dose delivery
11.  Computer Input Devices: Neutral Party or Source of Significant Error in Manual Lesion Segmentation? 
Journal of Digital Imaging  2010;24(1):135-141.
Lesion segmentation involves outlining the contour of an abnormality on an image to distinguish boundaries between normal and abnormal tissue and is essential to track malignant and benign disease in medical imaging for clinical, research, and treatment purposes. A laser optical mouse and a graphics tablet were used by radiologists to segment 12 simulated reference lesions per subject in two groups (one group comprised three lesion morphologies in two sizes, one for each input device for each device two sets of six, composed of three morphologies in two sizes each). Time for segmentation was recorded. Subjects completed an opinion survey following segmentation. Error in contour segmentation was calculated using root mean square error. Error in area of segmentation was calculated compared to the reference lesion. 11 radiologists segmented a total of 132 simulated lesions. Overall error in contour segmentation was less with the graphics tablet than with the mouse (P < 0.0001). Error in area of segmentation was not significantly different between the tablet and the mouse (P = 0.62). Time for segmentation was less with the tablet than the mouse (P = 0.011). All subjects preferred the graphics tablet for future segmentation (P = 0.011) and felt subjectively that the tablet was faster, easier, and more accurate (P = 0.0005). For purposes in which accuracy in contour of lesion segmentation is of the greater importance, the graphics tablet is superior to the mouse in accuracy with a small speed benefit. For purposes in which accuracy of area of lesion segmentation is of greater importance, the graphics tablet and mouse are equally accurate.
PMCID: PMC3046792  PMID: 20049624
Image segmentation; user-computer interface; computer assisted detection; computer hardware; data collection; human computer interaction; evaluation research; segmentation
12.  Medical data capture and display: the importance of clinicians' workstation design. 
The Department of Veterans Affairs is developing, testing and evaluating the benefits of physicians' workstations as an aid to medical data capture in an outpatient clinic setting. The physician's workstation uses a graphical user interface to aid the clinician in recording encounter data. Various input devices including keyboard, mouse, pen, voice, barcode reader, and tablet are available on the workstations, and user preferences will be examined. Access to general services such as electronic mail and reference databases is also available. The workstation provides a wide variety of patient specific data from the hospital information system, including image data. The single data collection process by the clinician will also provide data for the cost recovery process.
PMCID: PMC2247771  PMID: 7949987
13.  Stable Schizophrenia Patients Learn Equally Well as Age-Matched Controls and Better than Elderly Controls in Two Sensorimotor Rotary Pursuit Tasks 
Objective: To compare sensorimotor performance and learning in stable schizophrenia patients, healthy age- and sex-matched controls and elderly controls on two variations of the rotary pursuit: circle pursuit (true motor learning) and figure pursuit (motor and sequence learning).
Method: In the circle pursuit, a target circle, rotating with increasing speed along a predictable circular path on the computer screen, must be followed by a cursor controlled by a pen on a writing tablet. In the eight-trial figure pursuit, subjects learn to draw a complex figure by pursuing the target circle that moves along an invisible trajectory between and around several goals. Tasks were administered thrice (day 1, day 2, day 7) to 30 patients with stable schizophrenia (S), 30 healthy age- and sex-matched controls (C), and 30 elderly participants (>65 years; E) and recorded with a digitizing tablet and pressure-sensitive pen. The outcome measure accuracy (% of time that cursor is within the target) was used to assess performance.
Results: We observed significant group differences in accuracy, both in circle and figure pursuit tasks (E < S < C, p < 0.01). Strong learning effects were found in each group. Learning curves were similar in circle pursuit but differed between groups in figure pursuit. When corrected for group differences in starting level, the learning gains over the three sessions of schizophrenia patients and age-matched controls were equal and both were larger than those of the elderly controls.
Conclusion: Despite the reduced sensorimotor performance that was found in the schizophrenia patients, their sensorimotor learning seems to be preserved. The relevance of this finding for the evaluation of procedural learning in schizophrenia is discussed. The better performance and learning rate of the patients compared to the elderly controls was unexpected and deserves further study.
PMCID: PMC4241745  PMID: 25505425
rotor pursuit; schizophrenia; motor skills; learning curve; aging and cognitive function; procedural learning; motor learning
14.  A Hybrid Clustering Method for ROI Delineation in Small Animal Dynamic PET Images: Application to the Automatic Estimation of FDG Input Functions 
Tracer kinetic modeling with dynamic Positron Emission Tomography (PET) requires a plasma time-activity curve (PTAC) as an input function. Several image-derived input function (IDIF) methods that rely on drawing the region-of-interest (ROI) in large vascular structures have been proposed to overcome the problems caused by the invasive approach to obtaining the PTAC, especially for small animal studies. However, the manual placement of ROIs for estimating IDIF is subjective and labor-intensive, making it an undesirable and unreliable process. In this paper, we propose a novel hybrid clustering method (HCM) that objectively delineates ROIs in dynamic PET images for the estimation of IDIFs, and demonstrate its application to the mouse PET studies acquired with [18F]Fluoro-2-deoxy-2-D-glucose (FDG). We begin our HCM using K-means clustering for background removal. We then model the time-activity curves using polynomial regression mixture models in curve clustering for heart structure detection. The hierarchical clustering is finally applied for ROI refinements. The HCM achieved accurate ROI delineation in both computer simulations and experimental mouse studies. In the mouse studies the predicted IDIF had a high correlation with the gold standard, the PTAC derived from the invasive blood samples. The results indicate that the proposed HCM has a great potential in ROI delineation for automatic estimation of IDIF in dynamic FDG-PET studies.
PMCID: PMC3071356  PMID: 20952342
Position Emission Tomography (PET); curve clustering; segmentation; image-derived input function
15.  Feasibility of Concurrent Treatment with the Scanning Ultrasound Reflector Linear Array System (SURLAS) and the Helical Tomotherapy System 
To evaluate the feasibility of concurrent treatment with the Scanning Ultrasound Reflector Linear Array System (SURLAS) and helical tomotherapy (HT) intensity modulated radiation therapy (IMRT).
The SURLAS was placed on a RANDO phantom simulating a patient with superficial or deep recurrent breast cancer. A Megavoltage CT (MVCT) of the phantom with and without the SURLAS was obtained in the HT system. MVCT images with the SURLAS were obtained for two configurations: i) with the SURLAS' long axis parallel and ii) perpendicular to the longitudinal axis of the phantom. The MVCT simulation data set was then transferred to a radiation therapy planning station. Organs at risk (OAR) were contoured including the lungs, heart, abdomen and spinal cord. The metallic parts of the SURLAS were contoured as well and constraints were assigned to completely or directionally block radiation through them. The MVCT-simulation data set and regions of interest (ROI) files were subsequently transferred to the HT planning station. Several HT plans were obtained with optimization parameters that are usually used in the clinic. For comparison purposes, planning was also performed without the SURLAS on the phantom.
All plans with the SURLAS on the phantom showed adequate dose covering 95% of the planning target volume (PTV D95%), average dose and coefficient of variation of the planning target volume (PTV) dose distribution regardless of the SURLAS' orientation with respect to the RANDO phantom. Likewise, all OAR showed clinically acceptable dose values. Spatial dose distributions and dose-volume histogram (DVH) evaluation showed negligible plan degradation due to the presence of the SURLAS. Beam-on time varied depending on the selected optimization parameters.
From the perspective of the radiation dosage, concurrent treatment with the SURLAS and HT IMRT is feasible as demonstrated by the obtained clinically acceptable treatment plans. In addition, proper orientation of the SURLAS may be of benefit in reducing dose to organs at risk in some cases.
PMCID: PMC2879076  PMID: 18608592
SURLAS; helical tomotherapy; simultaneous thermoradiotherapy; IMRT; Megavoltage computed tomography
16.  Optimizing physician access to surgical intensive care unit laboratory information through mobile computing. 
Approximately 30 minutes of computer access time are required by surgical residents at Stanford University Medical Center (SUMC) to examine the lab values of all patients on a surgical intensive care unit (ICU) service, a task that must be performed several times a day. To reduce the time accessing this information and simultaneously increase the readability and currency of the data, we have created a mobile, pen-based user interface and software system that delivers lab results to surgeons in the ICU. The ScroungeMaster system, loaded on a portable tablet computer, retrieves lab results for a subset of patients from the central laboratory computer and stores them in a local database cache. The cache can be updated on command; this update takes approximately 2.7 minutes for all ICU patients being followed by the surgeon, and can be performed as a background task while the user continues to access selected lab results. The user interface presents lab results according to physiologic system. Which labs are displayed first is governed by a layout selection algorithm based on previous accesses to the patient's lab information, physician preferences, and the nature of the patient's medical condition. Initial evaluation of the system has shown that physicians prefer the ScroungeMaster interface to that of existing systems at SUMC and are satisfied with the system's performance. We discuss the evolution of ScroungeMaster and make observations on changes to physician work flow with the presence of mobile, pen-based computing in the ICU.
PMCID: PMC2233215  PMID: 8947778
17.  Detaching from the negative by reappraisal: the role of right superior frontal gyrus (BA9/32) 
The ability to reappraise the emotional impact of events is related to long-term mental health. Self-focused reappraisal (REAPPself), i.e., reducing the personal relevance of the negative events, has been previously associated with neural activity in regions near right medial prefrontal cortex, but rarely investigated among brain-damaged individuals. Thus, we aimed to examine the REAPPself ability of brain-damaged patients and healthy controls considering structural atrophies and gray matter intensities, respectively. Twenty patients with well-defined cortex lesions due to an acquired circumscribed tumor or cyst and 23 healthy controls performed a REAPPself task, in which they had to either observe negative stimuli or decrease emotional responding by REAPPself. Next, they rated the impact of negative arousal and valence. REAPPself ability scores were calculated by subtracting the negative picture ratings after applying REAPPself from the ratings of the observing condition. The scores of the patients were included in a voxel-based lesion-symptom mapping (VLSM) analysis to identify deficit related areas (ROI). Then, a ROI group-wise comparison was performed. Additionally, a whole-brain voxel-based-morphometry (VBM) analysis was run, in which healthy participant's REAPPself ability scores were correlated with gray matter intensities. Results showed that (1) regions in the right superior frontal gyrus (SFG), comprising the right dorsolateral prefrontal cortex (BA9) and the right dorsal anterior cingulate cortex (BA32), were associated with patient's impaired down-regulation of arousal, (2) a lesion in the depicted ROI occasioned significant REAPPself impairments, (3) REAPPself ability of controls was linked with increased gray matter intensities in the ROI regions. Our findings show for the first time that the neural integrity and the structural volume of right SFG regions (BA9/32) might be indispensable for REAPPself. Implications for neurofeedback research are discussed.
PMCID: PMC4023069  PMID: 24847230
emotion regulation; self-focused reappraisal; VLSM; VBM; right SFG
18.  Comparison of 3D MRI with high sampling efficiency and 2D multiplanar MRI for contouring in cervix cancer brachytherapy 
Radiology and Oncology  2012;46(3):242-251.
MRI sequences with short scanning times may improve accessibility of image guided adaptive brachytherapy (IGABT) of cervix cancer. We assessed the value of 3D MRI for contouring by comparing it to 2D multi-planar MRI.
Patients and methods
In 14 patients, 2D and 3D pelvic MRI were obtained at IGABT. High risk clinical target volume (HR CTV) was delineated by 2 experienced radiation oncologists, using the conventional (2D MRI-based) and test (3D MRI-based) approach. The value of 3D MRI for contouring was evaluated by using the inter-approach and inter-observer analysis of volumetric and topographic contouring uncertainties. To assess the magnitude of deviation from the conventional approach when using the test approach, the inter-approach analysis of contouring uncertainties was carried out for both observers. In addition, to assess reliability of 3D MRI for contouring, the impact of contouring approach on the magnitude of inter-observer delineation uncertainties was analysed.
No approach- or observer - specific differences in HR CTV sizes, volume overlap, or distances between contours were identified. When averaged over all delineated slices, the distances between contours in the inter-approach analysis were 2.6 (Standard deviation (SD) 0.4) mm and 2.8 (0.7) mm for observers 1 and 2, respectively. The magnitude of topographic and volumetric inter-observer contouring uncertainties, as obtained on the conventional approach, was maintained on the test approach. This variation was comparable to the inter-approach uncertainties with distances between contours of 3.1 (SD 0.8) and 3.0 (SD 0.7) mm on conventional and test approach, respectively. Variation was most pronounced at caudal HR CTV levels in both approaches and observers.
3D MRI could potentially replace multiplanar 2D MRI in cervix cancer IGABT, shortening the overall MRI scanning time and facilitating the contouring process, thus making this treatment method more widely employed.
PMCID: PMC3472953  PMID: 23077463
cervix cancer; brachytherapy; contouring; MRI
19.  Initial Experience and Evaluation of Reusable Insulin Pen Devices Among Patients with Diabetes in Emerging Countries 
Diabetes Therapy  2014;5(2):545-555.
Many individuals with type 2 diabetes in emerging countries are transitioning from vial-and-syringe insulin delivery to that of insulin pens (disposable or reusable). As with all insulin delivery methods, patient preferences and comfort are of utmost importance to optimize adherence to treatment. Patient-preferred characteristics for reusable insulin pens and barriers to appropriate injection, particularly in these regions, have not been widely reported in the clinical literature, highlighting a key information gap for clinicians considering these methods as part of a comprehensive diabetes management approach.
Face-to-face interviews were conducted with people with type 1/2 diabetes, including insulin-naïve and established insulin users. After moderator demonstration, participants were evaluated on their ability to perform a six-step process to inject a 10-unit dose into a pad with the AllStar® (AS; Sanofi, Mumbai, India), HumaPen Ergo II® (HE2; Eli Lilly, Indianapolis, USA), and NovoPen 4® (NP4; Novo Nordisk, Bagsværd, Denmark) pens. Local pens were also tested in India, China and Brazil.
A total of 503 people from India, Malaysia, Brazil, Egypt, and China participated. Participants completed the six-step process in an average, 2–3 min per pen. Participants ranked ease of overall use and ease of self-injection and dialing/reading dose as most important features for new insulin pens. When using the pens, the most difficult step was priming/safety testing, with 7–12% failing and 28–40% having difficulty; 6%, 18%, and 22% failed to hold the injection button down for the required period of time using AS, NP4, and HE2, respectively. Participants ranked AS significantly higher for nine of 12 ease-of-use features including three of the top four features considered the most important for reusable pens, while HE2 was ranked higher for two features. Local pens were ranked lowest.
Priming the pen and injecting the dose imparted most difficulty for people with diabetes in emerging countries. Most participants found AS easiest to use overall, with differences noted between pens for individual steps of dose delivery. Identifying characteristics most preferred by patients may assist in improving adherence to insulin therapy.
Electronic supplementary material
The online version of this article (doi:10.1007/s13300-014-0081-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4269642  PMID: 25213801
AllStar; Diabetes; HumaPen; Insulin; Insulin pens; NovoPen
20.  Hierarchical Anatomical Brain Networks for MCI Prediction: Revisiting Volumetric Measures 
PLoS ONE  2011;6(7):e21935.
Owning to its clinical accessibility, T1-weighted MRI (Magnetic Resonance Imaging) has been extensively studied in the past decades for prediction of Alzheimer's disease (AD) and mild cognitive impairment (MCI). The volumes of gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) are the most commonly used measurements, resulting in many successful applications. It has been widely observed that disease-induced structural changes may not occur at isolated spots, but in several inter-related regions. Therefore, for better characterization of brain pathology, we propose in this paper a means to extract inter-regional correlation based features from local volumetric measurements. Specifically, our approach involves constructing an anatomical brain network for each subject, with each node representing a Region of Interest (ROI) and each edge representing Pearson correlation of tissue volumetric measurements between ROI pairs. As second order volumetric measurements, network features are more descriptive but also more sensitive to noise. To overcome this limitation, a hierarchy of ROIs is used to suppress noise at different scales. Pairwise interactions are considered not only for ROIs with the same scale in the same layer of the hierarchy, but also for ROIs across different scales in different layers. To address the high dimensionality problem resulting from the large number of network features, a supervised dimensionality reduction method is further employed to embed a selected subset of features into a low dimensional feature space, while at the same time preserving discriminative information. We demonstrate with experimental results the efficacy of this embedding strategy in comparison with some other commonly used approaches. In addition, although the proposed method can be easily generalized to incorporate other metrics of regional similarities, the benefits of using Pearson correlation in our application are reinforced by the experimental results. Without requiring new sources of information, our proposed approach improves the accuracy of MCI prediction from (of conventional volumetric features) to (of hierarchical network features), evaluated using data sets randomly drawn from the ADNI (Alzheimer's Disease Neuroimaging Initiative) dataset.
PMCID: PMC3139571  PMID: 21818280
21.  Automatic segmentation of whole breast using an atlas approach and deformable image registration 
To compare inter-observer variations in delineating the whole breast for treatment planning using two contouring methods.
Methods and Materials
Auto-segmented contours were generated by a deformable image registration-based breast segmentation method (DEF-SEG) by mapping the whole breast clinical target volume (CTVwb) from a template case to a new patient case. Eight breast radiation oncologists modified the auto-segmented contours as necessary to achieve a clinically appropriate CTVwb and then recontoured the same case from scratch for comparison. Times to complete each approach as well as inter-observer variations were analyzed. The template case was also mapped to 10 breast cancer patients with body mass indexes ranging from 19.1 to 35.9. Three-dimensional surface-to-surface distances and volume overlapping analyses were computed to quantify contour variations.
The median time to edit the DEF-SEG-generated CTVwb was 12.9 min (range, 3.4–35.9), compared to 18.6 min (range, 8.9–45.2) to contour the CTVwb from scratch (30% faster; p = 0.028). The mean surface-to-surface distance was noticeably reduced from 1.6 mm among contours generated from scratch to 1.0 mm using the DEF-SEG method (p = 0.047). Deformed contours in 10 patients can achieve 94% volume overlap prior to correction and required editing of 5% of the contoured volume (range, 1%–10%).
Significant inter-observer variations suggest that there was a lack of consensus regarding the CTVwb, even among breast cancer specialists. Using the DEF-SEG method produced more consistent results and required less time. The DEF-SEG method can be successfully applied to patients with various body mass indexes.
PMCID: PMC2729433  PMID: 18804333
Auto-segmentation; Inter-observer variation; Target delineation; Breast contouring; Image-guided radiotherapy
22.  Conceptual Design and Simulation Study of an ROI-Focused Panel-PET Scanner 
PLoS ONE  2013;8(8):e72109.
Positron emission tomography (PET) is an important imaging modality for clincial use. Conventionally, the PET scanner is generally built to provide a roomy enough transverse field-of-view (FOV) for imaging most adults’ torsos. However, in many cases, the region-of-interest (ROI) for imaging is usually a small area inside the human body. Therefore, to fulfill a PET system which provides an FOV comparable in size to the target ROI seems appealing and more cost effective. Meanwhile, such a PET system has the potential for portable or bedside application with the reduced system size. In this work, we have investigated the feasibility of using dual-headed panel-detectors to build an ROI-focused PET scanner. A novel windowed list-mode ordered subset expectation maximization method was developed to perform the ROI image reconstruction. With this method, the ROI of the object can be reconstructed from the coincidences whose position determined by time-of-flight (TOF) measurements was inside the ROI. Monte Carlo simulation demonstrates the feasibility of detecting lesions not less than 1 cm in diameter, with a 300 ps full width at half maximum timing resolution. As a critical system performance, the impact of TOF information on image quality has been studied and the required TOF capability was assessed. With enhanced timing resolution, the distortions and artifacts were reduced effectively. The further improved TOF capability also shows a noticeable improvement of detection performance for low uptake lesions, as well as the recovery speed of lesion contrast, which is of practical significance in the lesion detection task.
PMCID: PMC3748112  PMID: 23977221
23.  Temporally Targeted Imaging Method Applied to ECG Gated Computed Tomography: Preliminary Phantom and In Vivo Experience 
Academic radiology  2008;15(1):93-106.
Rationale and Objectives
Existing cardiac imaging methods do not allow for improved temporal resolution when considering a targeted region of interest (ROI). The imaging method presented here enables improved temporal resolution for ROI imaging (namely, a reconstruction volume smaller than the complete field of view). Clinically, temporally targeted reconstruction would not change the primary means of reconstructing and evaluating images, but rather would enable the adjunct technique of ROI imaging, with improved temporal resolution compared with standard reconstruction (~20% smaller temporal scan window). In gated cardiac CT scans improved temporal resolution directly translates into a reduction in motion artifacts for rapidly moving objects such as the coronary arteries.
Materials and Methods
Retrospectively electrocardiogram gated coronary angiography data from a 64-slice CT system were utilized. A motion phantom simulating the motion profile of a coronary artery was constructed and scanned. Additionally, an in vivo study was performed using a porcine model. Comparisons between the new reconstruction technique and the standard reconstruction are given for an ROI centered on the right coronary artery, and a pulmonary ROI.
In both a well controlled motion model and a porcine model results show a decrease in motion induced artifacts including motion blur and streak artifacts from contrast enhanced vessels within the targeted ROIs, as assessed through both qualitative and quantitative observations.
Temporally targeted reconstruction techniques demonstrate the potential to reduce motion artifacts in coronary CT. Further study is warranted to demonstrate the conditions under which this technique will offer direct clinical utility. Improvement in temporal resolution for gated cardiac scans has implications for improving: contrast enhanced CT angiography, calcium scoring, and assessment of the pulmonary anatomy.
PMCID: PMC2693077  PMID: 18078912
Cardiac CT; Super-short Scan; Region-Of-Interest Imaging; Targeted Reconstruction
24.  A Randomized, Open-Label, Comparative Crossover Handling Trial between Two Durable Pens in Patients with Type 1 or 2 Diabetes Mellitus 
This open-label, randomized, comparative crossover usability study investigated preference between durable insulin pens, NovoPen® 4 and NovoPen 3, among patients with types 1 and 2 diabetes.
In a timed test, 82 current NovoPen 3 users (mean age, 48.5 years) assessed intuitiveness of NovoPen 4. After timed training, this group and 34 insulin-naïve patients (mean age, 61.8 years) were randomized to a handling evaluation of NovoPen 4 followed by NovoPen 3, or vice versa, in which participants made three injections into a foam cushion. A device-specific questionnaire was filled out for each pen. A third questionnaire asked participants to compare pens.
Current NovoPen 3 users completed the intuitive assessment of NovoPen 4 in an average time of 1.94 min (range, 0.57–4.98 min). The training of insulin-naïve patients occurred in slightly less time with NovoPen 4 than with NovoPen 3 but did not reach significance (9.9 versus 11.5 min; p = .32). Survey responses showed that both groups had less difficulty and were more confident in handling NovoPen 4 than NovoPen 3; 96.3% of the NovoPen 3 users and 100% of the insulin-naïve group preferred to use NovoPen 4 (p < .0001).
Patients currently using NovoPen 3 or who were insulin naïve expressed a preference for NovoPen 4 in this study, reporting it to be simpler to learn and easier to use than NovoPen 3. NovoPen 4 may help facilitate insulin therapy among newly diagnosed patients and potentially improve adherence and treatment satisfaction among current NovoPen 3 users.
PMCID: PMC3208884  PMID: 22027321
diabetes mellitus; insulin pen; NovoPen; preference
25.  Heuristic Evaluation and Usability Testing of a Computerized Patient-Reported Outcomes Survey for Headache Sufferers 
The aim of this study was to evaluate usability of a prototype tablet PC-administered computerized adaptive test (CAT) of headache impact and patient feedback report, referred to as HEADACHE-CAT.
Materials and Methods
Heuristic evaluation specialists (n = 2) formed a consensus opinion on the application's strengths and areas for improvement based on general usability principles and human factors research. Usability testing involved structured interviews with headache sufferers (n = 9) to assess how they interacted with and navigated through the application, and to gather input on the survey and report interface, content, visual design, navigation, instructions, and user preferences.
Specialists identified the need for improved instructions and text formatting, increased font size, page setup that avoids scrolling, and simplified presentation of feedback reports. Participants found the tool useful, and indicated a willingness to complete it again and recommend it to their healthcare provider. However, some had difficulty using the onscreen keyboard and autoadvance option; understanding the difference between generic and headache-specific questions; and interpreting score reports.
Heuristic evaluation and user testing can help identify usability problems in the early stages of application development, and improve the construct validity of electronic assessments such as the HEADACHE-CAT. An improved computerized HEADACHE-CAT measure can offer headache sufferers an efficient tool to increase patient self-awareness, monitor headaches over time, aid patient–provider communications, and improve quality of life.
PMCID: PMC3064878  PMID: 21214341
e-health; technology; telehealth; headache; health-related quality of life; patient-reported outcomes

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