Reproducibility of the Structural Brain Connectome Derived from Diffusion Tensor Imaging

Rationale

Disruptions of brain anatomical connectivity are believed to play a central role in several neurological and psychiatric illnesses. The structural brain connectome is typically derived from diffusion tensor imaging (DTI), which may be influenced by methodological factors related to signal processing, MRI scanners and biophysical properties of neuroanatomical regions. In this study, we evaluated how these variables affect the reproducibility of the structural connectome.

Methods

Twenty healthy adults underwent 3 MRI scanning sessions (twice in the same MRI scanner and a third time in a different scanner unit) within a short period of time. The scanning sessions included similar T1 weighted and DTI sequences. Deterministic or probabilistic tractography was performed to assess link weight based on the number of fibers connecting gray matter regions of interest (ROI). Link weight and graph theory network measures were calculated and reproducibility was assessed through intra-class correlation coefficients, assuming each scanning session as a rater.

Results

Connectome reproducibility was higher with data from the same scanner. The probabilistic approach yielded larger reproducibility, while the individual variation in the number of tracked fibers from deterministic tractography was negatively associated with reproducibility. Links connecting larger and anatomically closer ROIs demonstrated higher reproducibility. In general, graph theory measures demonstrated high reproducibility across scanning sessions.

Discussion

Anatomical factors and tractography approaches can influence the reproducibility of the structural connectome and should be factored in the interpretation of future studies. Our results demonstrate that connectome mapping is a largely reproducible technique, particularly as it relates to the geometry of network architecture measured by graph theory methods.     

Optic Radiation Fiber Tractography in Glioma Patients Based on High Angular Resolution Diffusion Imaging with Compressed Sensing Compared with Diffusion Tensor Imaging - Initial Experience

Objective

Up to now, fiber tractography in the clinical routine is mostly based on diffusion tensor imaging (DTI). However, there are known drawbacks in the resolution of crossing or kissing fibers and in the vicinity of a tumor or edema. These restrictions can be overcome by tractography based on High Angular Resolution Diffusion Imaging (HARDI) which in turn requires larger numbers of gradients resulting in longer acquisition times. Using compressed sensing (CS) techniques, HARDI signals can be obtained by using less non-collinear diffusion gradients, thus enabling the use of HARDI-based fiber tractography in the clinical routine.

Methods

Eight patients with gliomas in the temporal lobe, in proximity to the optic radiation (OR), underwent 3T MRI including a diffusion-weighted dataset with 30 gradient directions. Fiber tractography of the OR using a deterministic streamline algorithm based on DTI was compared to tractography based on reconstructed diffusion signals using HARDI+CS.

Results

HARDI+CS based tractography displayed the OR more conclusively compared to the DTI-based results in all eight cases. In particular, the potential of HARDI+CS-based tractography was observed for cases of high grade gliomas with significant peritumoral edema, larger tumor size or closer proximity of tumor and reconstructed fiber tract.

Conclusions

Overcoming the problem of long acquisition times, HARDI+CS seems to be a promising basis for fiber tractography of the OR in regions of disturbed diffusion, areas of high interest in glioma surgery.     

Tract specific reproducibility of tractography based morphology and diffusion metrics

Introduction

The reproducibility of tractography is important to determine its sensitivity to pathological abnormalities. The reproducibility of tract morphology has not yet been systematically studied and the recently developed tractography contrast Tract Density Imaging (TDI) has not yet been assessed at the tract specific level.

Materials and Methods

Diffusion tensor imaging (DTI) and probabilistic constrained spherical deconvolution (CSD) tractography are performed twice in 9 healthy subjects. Tractography is based on common space seed and target regions and performed for several major white matter tracts. Tractograms are converted to tract segmentations and inter-session reproducibility of tract morphology is assessed using Dice similarity coefficient (DSC). The coefficient of variation (COV) and intraclass correlation coefficient (ICC) are calculated of the following tract metrics: fractional anisotropy (FA), apparent diffusion coefficient (ADC), volume, and TDI. Analyses are performed both for proximal (deep white matter) and extended (including subcortical white matter) tract segmentations.

Results

Proximal DSC values were 0.70–0.92. DSC values were 5–10% lower in extended compared to proximal segmentations. COV/ICC values of FA, ADC, volume and TDI were 1–4%/0.65–0.94, 2–4%/0.62–0.94, 3–22%/0.53–0.96 and 8–31%/0.48–0.70, respectively, with the lower COV and higher ICC values found in the proximal segmentations.

Conclusion

For all investigated metrics, reproducibility depended on the segmented tract. FA and ADC had relatively low COV and relatively high ICC, indicating clinical potential. Volume had higher COV but its moderate to high ICC values in most tracts still suggest subject-differentiating power. Tract TDI had high COV and relatively low ICC, which reflects unfavorable reproducibility.     

Progressive Injury in Chronic Multiple Sclerosis Lesions Is Gender-Specific: A DTI Study

Objective

To evaluate the longitudinal integrity of white matter tracts in patients with relapsing remitting multiple sclerosis (RRMS) as determined by changes in diffusivity indices of lesional and non-lesional white matter in the optic radiation over 12 months.

Methods

The optic radiation (OR) was identified in sixty RRMS patients using probabilistic tractography. MS lesions were segmented on FLAIR T2 images and a lesion mask was intersected with the co-registered OR. Lesions within the OR were identified in 39 patients. Voxel-based analysis of axial diffusivity (AD) and radial diffusivity (RD) within OR lesions and non-lesional normal appearing white matter (NAWM) was performed at baseline and 12 months in 34 patients (five patients excluded due to new OR lesions).

Results

Both RD and AD demonstrated much higher values within the lesions compared with non-lesional NAWM. There was a significant (p<0.001) increase of lesional AD and RD during the follow-up period. This increase, however, was driven almost entirely by the male cohort, in which a significantly greater change in both AD (M-2.7%, F-0.9%) and RD (M-4.6%, F-0.7%) was observed during the follow-up period. Non-lesional NAWM also demonstrated an increase in both AD and RD, albeit on a much lesser scale (1.0% and 0.6% respectively). In contradistinction to lesions, the diffusivity change in non-lesional NAWM was similar between sexes.

Conclusions

The evolution of AD and RD in chronic MS lesions over 12 months suggests ongoing inflammatory demyelinating activity accompanied by axonal loss. In addition, our findings are consistent with the recently observed trend of more rapid clinical progression in males and establish a potential in vivo biomarker of gender dichotomy by demonstrating a significantly faster rate of microstructural change in the chronic lesions of male patients with MS.     

Evidence for altered basal ganglia-brainstem connections in cervical dystonia

Background

There has been increasing interest in the interaction of the basal ganglia with the cerebellum and the brainstem in motor control and movement disorders. In addition, it has been suggested that these subcortical connections with the basal ganglia may help to coordinate a network of regions involved in mediating posture and stabilization. While studies in animal models support a role for this circuitry in the pathophysiology of the movement disorder dystonia, thus far, there is only indirect evidence for this in humans with dystonia.

Methodology/Principal Findings

In the current study we investigated probabilistic diffusion tractography in DYT1-negative patients with cervical dystonia and matched healthy control subjects, with the goal of showing that patients exhibit altered microstructure in the connectivity between the pallidum and brainstem. The brainstem regions investigated included nuclei that are known to exhibit strong connections with the cerebellum. We observed large clusters of tractography differences in patients relative to healthy controls, between the pallidum and the brainstem. Tractography was decreased in the left hemisphere and increased in the right hemisphere in patients, suggesting a potential basis for the left/right white matter asymmetry we previously observed in focal dystonia patients.

Conclusions/Significance

These findings support the hypothesis that connections between the basal ganglia and brainstem play a role in the pathophysiology of dystonia.     

Target identification for stereotactic thalamotomy using diffusion tractography

Background

Stereotactic targets for thalamotomy are usually derived from population-based coordinates. Individual anatomy is used only to scale the coordinates based on the location of some internal guide points. While on conventional MR imaging the thalamic nuclei are indistinguishable, recently it has become possible to identify individual thalamic nuclei using different connectivity profiles, as defined by MR diffusion tractography.

Methodology and Principal Findings

Here we investigated the inter-individual variation of the location of target nuclei for thalamotomy: the putative ventralis oralis posterior (Vop) and the ventral intermedius (Vim) nucleus as defined by probabilistic tractography. We showed that the mean inter-individual distance of the peak Vop location is 7.33 mm and 7.42 mm for Vim. The mean overlap between individual Vop nuclei was 40.2% and it was 31.8% for Vim nuclei. As a proof of concept, we also present a patient who underwent Vop thalamotomy for untreatable tremor caused by traumatic brain injury and another patient who underwent Vim thalamotomy for essential tremor. The probabilistic tractography indicated that the successful tremor control was achieved with lesions in the Vop and Vim respectively.

Conclusions

Our data call attention to the need for a better appreciation of the individual anatomy when planning stereotactic functional neurosurgery.     

Abnormal Anatomical Connectivity between the Amygdala and Orbitofrontal Cortex in Conduct Disorder

Objective

Previous research suggested that structural and functional abnormalities within the amygdala and orbitofrontal cortex contribute to the pathophysiology of Conduct Disorder (CD). Here, we investigated whether the integrity of the white-matter pathways connecting these regions is abnormal and thus may represent a putative neurobiological marker for CD.

Methods

Diffusion Tensor Imaging (DTI) was used to investigate white-matter microstructural integrity in male adolescents with childhood-onset CD, compared with healthy controls matched in age, sex, intelligence, and socioeconomic status. Two approaches were employed to analyze DTI data: voxel-based morphometry of fractional anisotropy (FA), an index of white-matter integrity, and virtual dissection of white-matter pathways using tractography.

Results

Adolescents with CD displayed higher FA within the right external capsule relative to controls (T = 6.08, P<0.05, Family-Wise Error, whole-brain correction). Tractography analyses showed that FA values within the uncinate fascicle (connecting the amygdala and orbitofrontal cortex) were abnormally increased in individuals with CD relative to controls. This was in contrast with the inferior frontal-occipital fascicle, which showed no significant group differences in FA. The finding of increased FA in the uncinate fascicle remained significant when factoring out the contribution of attention-deficit/hyperactivity disorder symptoms. There were no group differences in the number of streamlines in either of these anatomical tracts.

Conclusions

These results provide evidence that CD is associated with white-matter microstructural abnormalities in the anatomical tract that connects the amygdala and orbitofrontal cortex, the uncinate fascicle. These results implicate abnormal maturation of white-matter pathways which are fundamental in the regulation of emotional behavior in CD.     

Altered Structural and Functional Connectivity in Late Preterm Preadolescence: An Anatomic Seed-Based Study of Resting State Networks Related to the Posteromedial and Lateral Parietal Cortex

Objective

Late preterm birth confers increased risk of developmental delay, academic difficulties and social deficits. The late third trimester may represent a critical period of development of neural networks including the default mode network (DMN), which is essential to normal cognition. Our objective is to identify functional and structural connectivity differences in the posteromedial cortex related to late preterm birth.

Methods

Thirty-eight preadolescents (ages 9–13; 19 born in the late preterm period (≥32 weeks gestational age) and 19 at term) without access to advanced neonatal care were recruited from a low socioeconomic status community in Brazil. Participants underwent neurocognitive testing, 3-dimensional T1-weighted imaging, diffusion-weighted imaging and resting state functional MRI (RS-fMRI). Seed-based probabilistic diffusion tractography and RS-fMRI analyses were performed using unilateral seeds within the posterior DMN (posterior cingulate cortex, precuneus) and lateral parietal DMN (superior marginal and angular gyri).

Results

Late preterm children demonstrated increased functional connectivity within the posterior default mode networks and increased anti-correlation with the central-executive network when seeded from the posteromedial cortex (PMC). Key differences were demonstrated between PMC components with increased anti-correlation with the salience network seen only with posterior cingulate cortex seeding but not with precuneus seeding. Probabilistic tractography showed increased streamlines within the right inferior longitudinal fasciculus and inferior fronto-occipital fasciculus within late preterm children while decreased intrahemispheric streamlines were also observed. No significant differences in neurocognitive testing were demonstrated between groups.

Conclusion

Late preterm preadolescence is associated with altered functional connectivity from the PMC and lateral parietal cortex to known distributed functional cortical networks despite no significant executive neurocognitive differences. Selective increased structural connectivity was observed in the setting of decreased posterior interhemispheric connections. Future work is needed to determine if these findings represent a compensatory adaptation employing alternate neural circuitry or could reflect subtle pathology resulting in emotional processing deficits not seen with neurocognitive testing.     

Microstructure and Cerebral Blood Flow within White Matter of the Human Brain: A TBSS Analysis

Background

White matter (WM) fibers connect different brain regions and are critical for proper brain function. However, little is known about the cerebral blood flow in WM and its relation to WM microstructure. Recent improvements in measuring cerebral blood flow (CBF) by means of arterial spin labeling (ASL) suggest that the signal in white matter may be detected. Its implications for physiology needs to be extensively explored. For this purpose, CBF and its relation to anisotropic diffusion was analyzed across subjects on a voxel-wise basis with tract-based spatial statistics (TBSS) and also across white matter tracts within subjects.

Methods

Diffusion tensor imaging and ASL were acquired in 43 healthy subjects (mean age = 26.3 years).

Results

CBF in WM was observed to correlate positively with fractional anisotropy across subjects in parts of the splenium of corpus callosum, the right posterior thalamic radiation (including the optic radiation), the forceps major, the right inferior fronto-occipital fasciculus, the right inferior longitudinal fasciculus and the right superior longitudinal fasciculus. Furthermore, radial diffusivity correlated negatively with CBF across subjects in similar regions. Moreover, CBF and FA correlated positively across white matter tracts within subjects.

Conclusion

The currently observed findings on a macroscopic level might reflect the metabolic demand of white matter on a microscopic level involving myelination processes or axonal function. However, the exact underlying physiological mechanism of this relationship needs further evaluation.     

Tractography delineates microstructural changes in the trigeminal nerve after focal radiosurgery for trigeminal neuralgia

Purpose

Focal radiosurgery is a common treatment modality for trigeminal neuralgia (TN), a neuropathic facial pain condition. Assessment of treatment effectiveness is primarily clinical, given the paucity of investigational tools to assess trigeminal nerve changes. Since diffusion tensor imaging (DTI) provides information on white matter microstructure, we explored the feasibility of trigeminal nerve tractography and assessment of DTI parameters to study microstructural changes after treatment. We hypothesized that trigeminal tractography provides more information than 2D-MR imaging, allowing detection of unique, focal changes in the target area after radiosurgery. Changes in specific diffusivities may provide insight into the mechanism of action of radiosurgery on the trigeminal nerve.

Methods and Materials

Five TN patients (4 females, 1 male, average age 67 years) treated with Gamma Knife radiosurgery, 80 Gy/100% isodose line underwent 3Tesla MR trigeminal nerve tractography before and sequentially up to fourteen months after treatment. Fractional anisotropy (FA), radial (RD) and axial (AD) diffusivities were calculated for the radiosurgical target area defined as the region-of-interest. Areas outside target and the contralateral nerve served as controls.

Results

Trigeminal tractography accurately detected the radiosurgical target. Radiosurgery resulted in 47% drop in FA values at the target with no significant change in FA outside the target, demonstrating highly focal changes after treatment. RD but not AD changed markedly, suggesting that radiosurgery primarily affects myelin. Tractography was more sensitive than conventional gadolinium-enhanced post-treatment MR, since FA changes were detected regardless of trigeminal nerve enhancement. In subjects with long term follow-up, recovery of FA/RD correlated with pain recurrence.

Conclusions

DTI parameters accurately detect the effects of focal radiosurgery on the trigeminal nerve, serving as an in vivo imaging tool to study TN. This study is a proof of principle for further assessment of DTI parameters to understand the pathophysiology of TN and treatment effects.     

Anisotropic Smoothing Improves DT-MRI-Based Muscle Fiber Tractography

Purpose

To assess the effect of anisotropic smoothing on fiber tracking measures, including pennation angle, fiber tract length, and fiber tract number in the medial gastrocnemius (MG) muscle in healthy subjects using diffusion-weighted magnetic resonance imaging (DW-MRI).

Materials and Methods

3T DW-MRI data were used for muscle fiber tractography in the MG of healthy subjects. Anisotropic smoothing was applied at three levels (5%, 10%, 15%), and pennation angle, tract length, fiber tract number, fractional anisotropy, and principal eigenvector orientation were quantified for each smoothing level.

Results

Fiber tract length increased with pre-fiber tracking smoothing, and local heterogeneities in fiber direction were reduced. However, pennation angle was not affected by smoothing.

Conclusion

Modest anisotropic smoothing (10%) improved fiber-tracking results, while preserving structural features.     

A Method for Accurate Reconstructions of the Upper Airway Using Magnetic Resonance Images

Objective

The purpose of this study is to provide an optimized method to reconstruct the structure of the upper airway (UA) based on magnetic resonance imaging (MRI) that can faithfully show the anatomical structure with a smooth surface without artificial modifications.

Methods

MRI was performed on the head and neck of a healthy young male participant in the axial, coronal and sagittal planes to acquire images of the UA. The level set method was used to segment the boundary of the UA. The boundaries in the three scanning planes were registered according to the positions of crossing points and anatomical characteristics using a Matlab program. Finally, the three-dimensional (3D) NURBS (Non-Uniform Rational B-Splines) surface of the UA was constructed using the registered boundaries in all three different planes.

Results

A smooth 3D structure of the UA was constructed, which captured the anatomical features from the three anatomical planes, particularly the location of the anterior wall of the nasopharynx. The volume and area of every cross section of the UA can be calculated from the constructed 3D model of UA.

Conclusions

A complete scheme of reconstruction of the UA was proposed, which can be used to measure and evaluate the 3D upper airway accurately.     

Estimating the Confidence Level of White Matter Connections Obtained with MRI Tractography

Background

Since the emergence of diffusion tensor imaging, a lot of work has been done to better understand the properties of diffusion MRI tractography. However, the validation of the reconstructed fiber connections remains problematic in many respects. For example, it is difficult to assess whether a connection is the result of the diffusion coherence contrast itself or the simple result of other uncontrolled parameters like for example: noise, brain geometry and algorithmic characteristics.

Methodology/Principal Findings

In this work, we propose a method to estimate the respective contributions of diffusion coherence versus other effects to a tractography result by comparing data sets with and without diffusion coherence contrast. We use this methodology to assign a confidence level to every gray matter to gray matter connection and add this new information directly in the connectivity matrix.

Conclusions/Significance

Our results demonstrate that whereas we can have a strong confidence in mid- and long-range connections obtained by a tractography experiment, it is difficult to distinguish between short connections traced due to diffusion coherence contrast from those produced by chance due to the other uncontrolled factors of the tractography methodology.     

Alteration of Fractional Anisotropy and Mean Diffusivity in Glaucoma: Novel Results of a Meta-Analysis of Diffusion Tensor Imaging Studies

Objectives

We hypothesized that a meta-analysis of existing studies may help to reveal significant changes on diffusion tensor imaging (DTI) in patients with glaucoma. Therefore, a meta-analysis was utilized to investigate the possibility that DTI can detect white matter damage in patients with glaucoma.

Methods

The study design and report adhered to the PRISMA Statement guidelines. DTI studies that compared glaucoma patients and controls were surveyed using PubMed, Web of Science and EMBASE (January 2008 to September 2013). Stata was used to analyze the decrease in fractional anisotropy (FA) and increase in mean diffusivity (MD) in the optic nerve and optic radiation in patients with glaucoma.

Results

Eleven DTI studies were identified through a comprehensive literature search, and 10 independent DTI studies of glaucoma patients were eligible for the meta-analysis. A random effects model revealed a significant FA reduction in the optic nerve and optic radiation, as well as a significant MD increase in the tracts. A heterogeneity analysis suggested that FA may be related to glaucoma severity.

Conclusions

Our findings revealed that the optic nerve and optic radiation were vulnerable regions in patients with glaucoma and that FA may be correlated with glaucoma severity and age. Furthermore, this study suggests that magnetic resonance imaging in patients with glaucoma may help to provide objective evidence to aid in the diagnosis and management of glaucoma.     

Utility and Limitation of Cumulative Stone Diameter in Predicting Urinary Stone Burden at Flexible Ureteroscopy with Holmium Laser Lithotripsy: A Single-Center Experience

Purpose

To retrospectively assess the clinical utility in ureteroscopy (URS) planning of cumulative stone diameter (CSD), which does not account for stone width or depth, as a predictor of URS outcome and compare it with stone volume.

Materials and Methods

Patients with renal stones treated at a single institute by flexible URS were retrospectively evaluated. To assess the clinical utility of CSD, relationships between stone-free (SF) status and stone burden (CSD and volume) were analyzed using the area under the receiver operating characteristics (AUROC) curve. To identify stone number impact on CSD, the AUROC of CSD divided by stone number was evaluated. Correlation coefficients of CSD and stone volume were also calculated for groups by stone number.

Results

In cases with CSD <20.0 mm, CSD and stone volume revealed equal ability to predict SF status. In cases with CSD ≥20.0 mm, stone volume showed higher predictive ability. The ROC curves for cases with ≥4 stones showed that CSD was less predictive of SF status than stone volume. The correlation coefficients of CSD and stone volume by stone number were 0.922 for 1 stone, 0.900 for 2–3 stones, and 0.661 for ≥4 stones.

Conclusions

In cases with CSD ≥20.0 mm or ≥4 stones, we should evaluate stone volume for a more predictive stone burden, and pretreatment non-contrast CT seems sufficient. In cases with CSD <20.0 mm or 1–3 stones, CSD was as valid a predictor of preoperative stone burden as stone volume, so preoperative kidney-ureter-bladder (KUB) films may be sufficient.     

Retinal Nerve Fiber and Optic Disc Morphology in Patients with Human Immunodeficiency Virus Using the Heidelberg Retina Tomography 3

Purpose

To use novel confocal scanning ophthalmoscopy technology to test hypothesis that HIV-seropositive patients without history of retinitis with a history of a low CD4 count are more likely to have damage to their retinal nerve fiber layer (RNFL) when compared to patients with high CD4 count. In addition, we compared optic disc morphologic changes with glaucoma.

Design

Cross-sectional study.

Participants and Controls

171 patients were divided into four groups. The control group consisted of 40 eyes of 20 HIV-seronegative patients. The second group consisted of 80 eyes of 41 HIV-positive patients whose CD4 cell count never dropped below 100 (1.0 x 10⁹/L). The third group consisted of 44 eyes of 26 HIV-positive patients with a history of low CD4 counts <100. Fourth group consisted of 79 eyes of 79 patients with confirmed glaucoma who served as positive controls.

Testing

Confocal scanning laser ophthalmoscopy was performed with the Heidelberg Retina Tomograph (HRT3) and data were analyzed with HRT3, software (Heyex version 1.5.10.0).

Main Outcome Measures

Disc area, cup area, cup volume, rim volume, mean cup depth, maximum cup depth, cup-to-disc ration, mean RNFL thickness, and RNFL cross-sectional area.

Results

Analysis of the global optic nerve and cup parameters showed no difference in disk area among the four groups. There was also no difference in cup, rim volume, mean cup depth, or maximum cup depth among the first three groups but they were all different from glaucoma group. The RNFL was thinner in glaucoma and both HIV-positive groups compared to HIV-seronegative subjects. The cross sectional RNFL area was thinner in both high and low CD4 HIV-positive groups compared to HIV-seronegative group in the nasal and temporal/inferior sectors, respectively. Glaucoma group showed thinning in all sectors.

Conclusions

HIV retinopathy results in retinal nerve fiber layer loss without structural optic nerve supportive tissue change. RNFL damage may occur early in HIV disease by mechanism different than in glaucoma.     

Corticospinal tract-sparing intensity-modulated radiotherapy treatment planning

Aim

To establish intensity-modulated radiotherapy (IMRT) planning procedures that spare the corticospinal tract by integrating diffusion tensor tractography into the treatment planning software.

Background

Organs at risk are generally contoured according to the outline of the organ as demonstrated by CT or MRI. But a part of the organ with specific function is difficult to protect, because such functional part of the organ cannot be delineated on CT or conventional sequence of MRI.

Methods

Diagnostic and treatment planning images of glioblastoma patients who had been treated by conventional 3-dimensional conformal radiotherapy were used for re-planning of IMRT. Three-dimensional fiber maps of the corticospinal tracts were created from the diffusion tensors obtained from the patients before the surgery, and were blended with the anatomical MR images (i.e. gadolinium-enhanced T1-weighted images or T2-weighted images). DICOM-formatted blended images were transferred and fused to the planning CT images. Then, IMRT plans were attempted.

Results

The corticospinal tracts could be contoured as organs at risk (OARs), because the blended images contained both anatomical information and fiber-tract maps. Other OARs were contoured in a way similar to that of ordinary IMRT planning. Gross tumor volumes, clinical target volumes, planning target volumes, and other OARs were contoured on the treatment planning software, and IMRT plans were made.

Conclusions

IMRT plans with diminished doses to the corticospinal tract were attained. This technique enabled us to spare specific neuron fibers as OARs which were formerly “invisible” and to reduce the probability of late morbidities.     

Extrapolation-Based References Improve Motion and Eddy-Current Correction of High B-Value DWI Data: Application in Parkinson’s Disease Dementia

Purpose

Conventional motion and eddy-current correction, where each diffusion-weighted volume is registered to a non diffusion-weighted reference, suffers from poor accuracy for high b-value data. An alternative approach is to extrapolate reference volumes from low b-value data. We aim to compare the performance of conventional and extrapolation-based correction of diffusional kurtosis imaging (DKI) data, and to demonstrate the impact of the correction approach on group comparison studies.

Methods

DKI was performed in patients with Parkinson’s disease dementia (PDD), and healthy age-matched controls, using b-values of up to 2750 s/mm². The accuracy of conventional and extrapolation-based correction methods was investigated. Parameters from DTI and DKI were compared between patients and controls in the cingulum and the anterior thalamic projection tract.

Results

Conventional correction resulted in systematic registration errors for high b-value data. The extrapolation-based methods did not exhibit such errors, yielding more accurate tractography and up to 50% lower standard deviation in DKI metrics. Statistically significant differences were found between patients and controls when using the extrapolation-based motion correction that were not detected when using the conventional method.

Conclusion

We recommend that conventional motion and eddy-current correction should be abandoned for high b-value data in favour of more accurate methods using extrapolation-based references.     

3D Topography of the Young Adult Anal Sphincter Complex Reconstructed from Undeformed Serial Anatomical Sections

Background

Pelvic-floor anatomy is usually studied by artifact-prone dissection or imaging, which requires prior anatomical knowledge. We used the serial-section approach to settle contentious issues and an interactive 3D-pdf to make the results widely accessible.

Method

3D reconstructions of undeformed thin serial anatomical sections of 4 females and 2 males (21–35y) of the Chinese Visible Human database.

Findings

Based on tendinous septa and muscle-fiber orientation as segmentation guides, the anal-sphincter complex (ASC) comprised the subcutaneous external anal sphincter (EAS) and the U-shaped puborectal muscle, a part of the levator ani muscle (LAM). The anococcygeal ligament fixed the EAS to the coccygeal bone. The puborectal-muscle loops, which define the levator hiatus, passed around the anorectal junction and inserted anteriorly on the perineal body and pubic bone. The LAM had a common anterior attachment to the pubic bone, but separated posteriorly into puborectal and “pubovisceral” muscles. This pubovisceral muscle was bilayered: its internal layer attached to the conjoint longitudinal muscle of the rectum and the rectococcygeal fascia, while its outer, patchy layer reinforced the inner layer. ASC contraction makes the ano-rectal bend more acute and lifts the pelvic floor. Extensions of the rectal longitudinal smooth muscle to the coccygeal bone (rectococcygeal muscle), perineal body (rectoperineal muscle), and endopelvic fascia (conjoint longitudinal and pubovisceral muscles) formed a “diaphragm” at the inferior boundary of the mesorectum that suspended the anorectal junction. Its contraction should straighten the anorectal bend.

Conclusion

The serial-section approach settled contentious topographic issues of the pelvic floor. We propose that the ASC is involved in continence and the rectal diaphragm in defecation.     

Cost-Effectiveness Analysis of Endoscopic Ultrasound versus Magnetic Resonance Cholangiopancreatography in Patients with Suspected Common Bile Duct Stones

Background

Patients with suspected common bile duct (CBD) stones are often diagnosed using endoscopic retrograde cholangiopancreatography (ERCP), an invasive procedure with risk of significant complications. Using endoscopic ultrasound (EUS) or Magnetic Resonance CholangioPancreatography (MRCP) first to detect CBD stones can reduce the risk of unnecessary procedures, cut complications and may save costs.

Aim

This study sought to compare the cost-effectiveness of initial EUS or MRCP in patients with suspected CBD stones.

Methods

This study is a model based cost-utility analysis estimating mean costs and quality-adjusted life years (QALYs) per patient from the perspective of the UK National Health Service (NHS) over a 1 year time horizon. A decision tree model was constructed and populated with probabilities, outcomes and cost data from published sources, including one-way and probabilistic sensitivity analyses.

Results

Using MRCP to select patients for ERCP was less costly than using EUS to select patients or proceeding directly to ERCP ($1299 versus $1753 and $1781, respectively), with similar QALYs accruing to each option (0.998, 0.998 and 0.997 for EUS, MRCP and direct ERCP, respectively). Initial MRCP was the most cost-effective option with the highest monetary net benefit, and this result was not sensitive to model parameters. MRCP had a 61% probability of being cost-effective at $29,000, the maximum willingness to pay for a QALY commonly used in the UK.

Conclusion

From the perspective of the UK NHS, MRCP was the most cost-effective test in the diagnosis of CBD stones.