Publications by Year: 2020

Kyriakos Dalamagkas, Magdalini Tsintou, Yogesh Rathi, Lauren J O'Donnell, Ofer Pasternak, Xue Gong, Anne Zhu, Peter Savadjiev, George M Papadimitriou, Marek Kubicki, Edward H Yeterian, and Nikos Makris. 6/2020. “Individual Variations of the Human Corticospinal Tract and Its Hand-Related Motor Fibers Using Diffusion MRI Tractography.” Brain Imaging Behav, 14, 3, Pp. 696-714.Abstract
The corticospinal tract (CST) is one of the most well studied tracts in human neuroanatomy. Its clinical significance can be demonstrated in many notable traumatic conditions and diseases such as stroke, spinal cord injury (SCI) or amyotrophic lateral sclerosis (ALS). With the advent of diffusion MRI and tractography the computational representation of the human CST in a 3D model became available. However, the representation of the entire CST and, specifically, the hand motor area has remained elusive. In this paper we propose a novel method, using manually drawn ROIs based on robustly identifiable neuroanatomic structures to delineate the entire CST and isolate its hand motor representation as well as to estimate their variability and generate a database of their volume, length and biophysical parameters. Using 37 healthy human subjects we performed a qualitative and quantitative analysis of the CST and the hand-related motor fiber tracts (HMFTs). Finally, we have created variability heat maps from 37 subjects for both the aforementioned tracts, which could be utilized as a reference for future studies with clinical focus to explore neuropathology in both trauma and disease states.
Björn Lampinen, Filip Szczepankiewicz, Johan Mårtensson, Danielle van Westen, Oskar Hansson, Carl-Fredrik Westin, and Markus Nilsson. 9/2020. “Towards Unconstrained Compartment Modeling in White Matter Using Diffusion-Relaxation MRI with Tensor-Valued Diffusion Encoding.” Magn Reson Med, 84, 3, Pp. 1605-23.Abstract
PURPOSE: To optimize diffusion-relaxation MRI with tensor-valued diffusion encoding for precise estimation of compartment-specific fractions, diffusivities, and T values within a two-compartment model of white matter, and to explore the approach in vivo. METHODS: Sampling protocols featuring different b-values (b), b-tensor shapes (b ), and echo times (TE) were optimized using Cramér-Rao lower bounds (CRLB). Whole-brain data were acquired in children, adults, and elderly with white matter lesions. Compartment fractions, diffusivities, and T values were estimated in a model featuring two microstructural compartments represented by a "stick" and a "zeppelin." RESULTS: Precise parameter estimates were enabled by sampling protocols featuring seven or more "shells" with unique b/b /TE-combinations. Acquisition times were approximately 15 minutes. In white matter of adults, the "stick" compartment had a fraction of approximately 0.5 and, compared with the "zeppelin" compartment, featured lower isotropic diffusivities (0.6 vs. 1.3 μm /ms) but higher T values (85 vs. 65 ms). Children featured lower "stick" fractions (0.4). White matter lesions exhibited high "zeppelin" isotropic diffusivities (1.7 μm /ms) and T values (150 ms). CONCLUSIONS: Diffusion-relaxation MRI with tensor-valued diffusion encoding expands the set of microstructure parameters that can be precisely estimated and therefore increases their specificity to biological quantities.
Joseph M Gullett, Andrew O'Shea, Damon G Lamb, Eric C Porges, Deirdre M O'Shea, Ofer Pasternak, Ronald A Cohen, and Adam J Woods. 6/2020. “The Association of White Matter Free Water With Cognition in Older Adults.” Neuroimage, 219, Pp. 117040.Abstract
BACKGROUND: Extracellular free water within cerebral white matter tissue has been shown to increase with age and pathology, yet the cognitive consequences of free water in typical aging prior to the development of neurodegenerative disease remains unclear. Understanding the contribution of free water to cognitive function in older adults may provide important insight into the neural mechanisms of the cognitive aging process. METHODS: A diffusion-weighted MRI measure of extracellular free water as well as a commonly used diffusion MRI metric (fractional anisotropy) along nine bilateral white matter pathways were examined for their relationship with cognitive function assessed by the NIH Toolbox Cognitive Battery in 47 older adults (mean age ​= ​74.4 years, SD ​= ​5.4 years, range ​= ​65-85 years). Probabilistic tractography at the 99th percentile level of probability (Tracts Constrained by Underlying Anatomy; TRACULA) was utilized to produce the pathways on which microstructural characteristics were overlaid and examined for their contribution to cognitive function independent of age, education, and gender. RESULTS: When examining the 99th percentile probability core white matter pathway derived from TRACULA, poorer fluid cognitive ability was related to higher mean free water values across the angular and cingulum bundles of the cingulate gyrus, as well as the corticospinal tract and the superior longitudinal fasciculus. There was no relationship between cognition and mean FA or free water-adjusted FA across the 99th percentile core white matter pathway. Crystallized cognitive ability was not associated with any of the diffusion measures. When examining cognitive domains comprising the NIH Toolbox Fluid Cognition index relationships with these white matter pathways, mean free water demonstrated strong hemispheric and functional specificity for cognitive performance, whereas mean FA was not related to age or cognition across the 99th percentile pathway. CONCLUSIONS: Extracellular free water within white matter appears to increase with normal aging, and higher values are associated with significantly lower fluid but not crystallized cognitive functions. When using TRACULA to estimate the core of a white matter pathway, a higher degree of free water appears to be highly specific to the pathways associated with memory, working memory, and speeded decision-making performance, whereas no such relationship existed with FA. These data suggest that free water may play an important role in the cognitive aging process, and may serve as a stronger and more specific indicator of early cognitive decline than traditional diffusion MRI measures, such as FA.
Esra Abaci Turk, Mazdak S Abulnaga, Jie Luo, Jeffrey N Stout, Henry A Feldman, Ata Turk, Borjan Gagoski, Lawrence L Wald, Elfar Adalsteinsson, Drucilla J Roberts, Carolina Bibbo, Julian N Robinson, Polina Golland, Ellen P Grant, and William H Barth. 4/2020. “Placental MRI: Effect of Maternal Position and Uterine Contractions on Placental BOLD MRI Measurements.” Placenta, 95, Pp. 69-77.Abstract
INTRODUCTION: Before using blood-oxygen-level-dependent magnetic resonance imaging (BOLD MRI) during maternal hyperoxia as a method to detect individual placental dysfunction, it is necessary to understand spatiotemporal variations that represent normal placental function. We investigated the effect of maternal position and Braxton-Hicks contractions on estimates obtained from BOLD MRI of the placenta during maternal hyperoxia. METHODS: For 24 uncomplicated singleton pregnancies (gestational age 27-36 weeks), two separate BOLD MRI datasets were acquired, one in the supine and one in the left lateral maternal position. The maternal oxygenation was adjusted as 5 min of room air (21% O), followed by 5 min of 100% FiO. After datasets were corrected for signal non-uniformities and motion, global and regional BOLD signal changes in R* and voxel-wise Time-To-Plateau (TTP) in the placenta were measured. The overall placental and uterine volume changes were determined across time to detect contractions. RESULTS: In mothers without contractions, increases in global placental R* in the supine position were larger compared to the left lateral position with maternal hyperoxia. Maternal position did not alter global TTP but did result in regional changes in TTP. 57% of the subjects had Braxton-Hicks contractions and 58% of these had global placental R* decreases during the contraction. CONCLUSION: Both maternal position and Braxton-Hicks contractions significantly affect global and regional changes in placental R* and regional TTP. This suggests that both factors must be taken into account in analyses when comparing placental BOLD signals over time within and between individuals.
Petrea Frid, M Drake, Anne-Katrin Giese, Johan Wasselius, Markus D Schirmer, Kathleen L Donahue, Lisa Cloonan, Robert Irie, Elissa C McIntosh, and Polina Golland. 3/2020. “Detailed Phenotyping of Posterior vs. Anterior Circulation Ischemic Stroke: A Multi-center MRI Study.” J Neurol, 267, 3, Pp. 649-58.Abstract


Posterior circulation ischemic stroke (PCiS) constitutes 20-30% of ischemic stroke cases. Detailed information about differences between PCiS and anterior circulation ischemic stroke (ACiS) remains scarce. Such information might guide clinical decision making and prevention strategies. We studied risk factors and ischemic stroke subtypes in PCiS vs. ACiS and lesion location on magnetic resonance imaging (MRI) in PCiS.


Out of 3,301 MRIs from 12 sites in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN), we included 2,381 cases with acute DWI lesions. The definition of ACiS or PCiS was based on lesion location. We compared the groups using Chi-squared and logistic regression.


PCiS occurred in 718 (30%) patients and ACiS in 1663 (70%). Diabetes and male sex were more common in PCiS vs. ACiS (diabetes 27% vs. 23%, p < 0.05; male sex 68% vs. 58%, p < 0.001). Both were independently associated with PCiS (diabetes, OR = 1.29; 95% CI 1.04-1.61; male sex, OR = 1.46; 95% CI 1.21-1.78). ACiS more commonly had large artery atherosclerosis (25% vs. 20%, p < 0.01) and cardioembolic mechanisms (17% vs. 11%, p < 0.001) compared to PCiS. Small artery occlusion was more common in PCiS vs. ACiS (20% vs. 14%, p < 0.001). Small artery occlusion accounted for 47% of solitary brainstem infarctions.


Ischemic stroke subtypes differ between the two phenotypes. Diabetes and male sex have a stronger association with PCiS than ACiS. Definitive MRI-based PCiS diagnosis aids etiological investigation and contributes additional insights into specific risk factors and mechanisms of injury in PCiS.

Ørjan Bergmann, Rafael Henriques, Carl-Fredrik Westin, and Ofer Pasternak. 3/2020. “Fast and Accurate Initialization of the Free-water Imaging Model Parameters from Multi-shell Diffusion MRI.” NMR Biomed, 33, 3, Pp. e4219.Abstract
Cerebrospinal fluid partial volume effect is a known bias in the estimation of Diffusion Tensor Imaging (DTI) parameters from diffusion MRI data. The Free-Water Imaging model for diffusion MRI data adds a second compartment to the DTI model, which explicitly accounts for the signal contribution of extracellular free-water, such as cerebrospinal fluid. As a result the DTI parameters obtained through the free-water model are corrected for partial volume effects, and thus better represent tissue microstructure. In addition, the model estimates the fractional volume of free-water, and can be used to monitor changes in the extracellular space. Under certain assumptions, the model can be estimated from single-shell diffusion MRI data. However, by using data from multi-shell diffusion acquisitions, these assumptions can be relaxed, and the fit becomes more robust. Nevertheless, fitting the model to multi-shell data requires high computational cost, with a non-linear iterative minimization, which has to be initialized close enough to the global minimum to avoid local minima and to robustly estimate the model parameters. Here we investigate the properties of the main initialization approaches that are currently being used, and suggest new fast approaches to improve the initial estimates of the model parameters. We show that our proposed approaches provide a fast and accurate initial approximation of the model parameters, which is very close to the final solution. We demonstrate that the proposed initializations improve the final outcome of non-linear model fitting.
Lipeng Ning, Borjan Gagoski, Filip Szczepankiewicz, Carl-Fredrik Westin, and Yogesh Rathi. 3/2020. “Joint RElaxation-Diffusion Imaging Moments to Probe Neurite Microstructure.” IEEE Trans Med Imaging, 39, 3, Pp. 668-77.Abstract
Joint relaxation-diffusion measurements can provide new insight about the tissue microstructural properties. Most recent methods have focused on inverting the Laplace transform to recover the joint distribution of relaxation-diffusion. However, as is well-known, this problem is notoriously ill-posed and numerically unstable. In this work, we address this issue by directly computing the joint moments of transverse relaxation rate and diffusivity, which can be robustly estimated. To zoom into different parts of the joint distribution, we further enhance our method by applying multiplicative filters to the joint probability density function of relaxation and diffusion and compute the corresponding moments. We propose an approach to use these moments to compute several novel scalar indices to characterize specific properties of the underlying tissue microstructure. Furthermore, for the first time, we propose an algorithm to estimate diffusion signals that are independent of echo time based on the moments of the marginal probability density function of diffusion. We demonstrate its utility in extracting tissue information not contaminated with multiple intra-voxel relaxation rates. We compare the performance of four types of filters that zoom into tissue components with different relaxation and diffusion properties and demonstrate it on an in-vivo human dataset. Experimental results show that these filters are able to characterize heterogeneous tissue microstructure. Moreover, the filtered diffusion signals are also able to distinguish fiber bundles with similar orientations but different relaxation rates. The proposed method thus allows to characterize the neural microstructure information in a robust and unique manner not possible using existing techniques.
Fan Zhang, Thomas Noh, Parikshit Juvekar, Sarah F Frisken, Laura Rigolo, Isaiah Norton, Tina Kapur, Sonia Pujol, William Wells, Alex Yarmarkovich, Gordon Kindlmann, Demian Wassermann, Raul San Jose Estepar, Yogesh Rathi, Ron Kikinis, Hans J Johnson, Carl-Fredrik Westin, Steve Pieper, Alexandra J Golby, and Lauren J O'Donnell. 3/2020. “SlicerDMRI: Diffusion MRI and Tractography Research Software for Brain Cancer Surgery Planning and Visualization.” JCO Clin Cancer Inform, 4, Pp. 299-309.Abstract
PURPOSE: We present SlicerDMRI, an open-source software suite that enables research using diffusion magnetic resonance imaging (dMRI), the only modality that can map the white matter connections of the living human brain. SlicerDMRI enables analysis and visualization of dMRI data and is aimed at the needs of clinical research users. SlicerDMRI is built upon and deeply integrated with 3D Slicer, a National Institutes of Health-supported open-source platform for medical image informatics, image processing, and three-dimensional visualization. Integration with 3D Slicer provides many features of interest to cancer researchers, such as real-time integration with neuronavigation equipment, intraoperative imaging modalities, and multimodal data fusion. One key application of SlicerDMRI is in neurosurgery research, where brain mapping using dMRI can provide patient-specific maps of critical brain connections as well as insight into the tissue microstructure that surrounds brain tumors. PATIENTS AND METHODS: In this article, we focus on a demonstration of SlicerDMRI as an informatics tool to enable end-to-end dMRI analyses in two retrospective imaging data sets from patients with high-grade glioma. Analyses demonstrated here include conventional diffusion tensor analysis, advanced multifiber tractography, automated identification of critical fiber tracts, and integration of multimodal imagery with dMRI. RESULTS: We illustrate the ability of SlicerDMRI to perform both conventional and advanced dMRI analyses as well as to enable multimodal image analysis and visualization. We provide an overview of the clinical rationale for each analysis along with pointers to the SlicerDMRI tools used in each. CONCLUSION: SlicerDMRI provides open-source and clinician-accessible research software tools for dMRI analysis. SlicerDMRI is available for easy automated installation through the 3D Slicer Extension Manager.
Christian Wachinger, Matthew Toews, Georg Langs, William Wells, and Polina Golland. 2/2020. “Keypoint Transfer for Fast Whole-Body Segmentation.” IEEE Trans Med Imaging, 39, 2, Pp. 273-82.Abstract
We introduce an approach for image segmentation based on sparse correspondences between keypoints in testing and training images. Keypoints represent automatically identified distinctive image locations, where each keypoint correspondence suggests a transformation between images. We use these correspondences to transfer label maps of entire organs from the training images to the test image. The keypoint transfer algorithm includes three steps: (i) keypoint matching, (ii) voting-based keypoint labeling, and (iii) keypoint-based probabilistic transfer of organ segmentations. We report segmentation results for abdominal organs in whole-body CT and MRI, as well as in contrast-enhanced CT and MRI. Our method offers a speed-up of about three orders of magnitude in comparison to common multi-atlas segmentation, while achieving an accuracy that compares favorably. Moreover, keypoint transfer does not require the registration to an atlas or a training phase. Finally, the method allows for the segmentation of scans with highly variable field-of-view.
Samo Lasič, Filip Szczepankiewicz, Erica Dall'Armellina, Arka Das, Christopher Kelly, Sven Plein, Jürgen E Schneider, Markus Nilsson, and Irvin Teh. 2/2020. “Motion-compensated b-tensor Encoding for in vivo Cardiac Diffusion-weighted Imaging.” NMR Biomed, 33, 2, Pp. e4213.Abstract
Motion is a major confound in diffusion-weighted imaging (DWI) in the body, and it is a common cause of image artefacts. The effects are particularly severe in cardiac applications, due to the nonrigid cyclical deformation of the myocardium. Spin echo-based DWI commonly employs gradient moment-nulling techniques to desensitise the acquisition to velocity and acceleration, ie, nulling gradient moments up to the 2nd order (M2-nulled). However, current M2-nulled DWI scans are limited to encode diffusion along a single direction at a time. We propose a method for designing b-tensors of arbitrary shapes, including planar, spherical, prolate and oblate tensors, while nulling gradient moments up to the 2nd order and beyond. The design strategy comprises initialising the diffusion encoding gradients in two encoding blocks about the refocusing pulse, followed by appropriate scaling and rotation, which further enables nulling undesired effects of concomitant gradients. Proof-of-concept assessment of in vivo mean diffusivity (MD) was performed using linear and spherical tensor encoding (LTE and STE, respectively) in the hearts of five healthy volunteers. The results of the M2-nulled STE showed that (a) the sequence was robust to cardiac motion, and (b) MD was higher than that acquired using standard M2-nulled LTE, where diffusion-weighting was applied in three orthogonal directions, which may be attributed to the presence of restricted diffusion and microscopic diffusion anisotropy. Provided adequate signal-to-noise ratio, STE could significantly shorten estimation of MD compared with the conventional LTE approach. Importantly, our theoretical analysis and the proposed gradient waveform design may be useful in microstructure imaging beyond diffusion tensor imaging where the effects of motion must be suppressed.
Maria Angelique Di Biase, Fan Zhang, Amanda Lyall, Marek Kubicki, René CW Mandl, Iris E Sommer, and Ofer Pasternak. 2/2020. “Neuroimaging Auditory Verbal Hallucinations in Schizophrenia Patient and Healthy Populations.” Psychol Med, 50, 3, Pp. 403-12.Abstract
BACKGROUND: Auditory verbal hallucinations (AVH) are a cardinal feature of schizophrenia, but they can also appear in otherwise healthy individuals. Imaging studies implicate language networks in the generation of AVH; however, it remains unclear if alterations reflect biologic substrates of AVH, irrespective of diagnostic status, age, or illness-related factors. We applied multimodal imaging to identify AVH-specific pathology, evidenced by overlapping gray or white matter deficits between schizophrenia patients and healthy voice-hearers. METHODS: Diffusion-weighted and T1-weighted magnetic resonance images were acquired in 35 schizophrenia patients with AVH (SCZ-AVH), 32 healthy voice-hearers (H-AVH), and 40 age- and sex-matched controls without AVH. White matter fractional anisotropy (FA) and gray matter thickness (GMT) were computed for each region comprising ICBM-DTI and Desikan-Killiany atlases, respectively. Regions were tested for significant alterations affecting both SCZ-AVH and H-AVH groups, relative to controls. RESULTS: Compared with controls, the SCZ-AVH showed widespread FA and GMT reductions; but no significant differences emerged between H-AVH and control groups. While no overlapping pathology appeared in the overall study groups, younger (<40 years) H-AVH and SCZ-AVH subjects displayed overlapping FA deficits across four regions (p < 0.05): the genu and splenium of the corpus callosum, as well as the anterior limbs of the internal capsule. Analyzing these regions with free-water imaging ascribed overlapping FA abnormalities to tissue-specific anisotropy changes. CONCLUSIONS: We identified white matter pathology associated with the presence of AVH, independent of diagnostic status. However, commonalities were constrained to younger and more homogenous groups, after reducing pathologic variance associated with advancing age and chronicity effects.
Christian Herz, Kemal Tuncali, Andriy Fedorov, Kyle MacNeil, Peter A Behringer, Junichi Tokuda, Alireza Mehrtash, Parvin Mousavi, Ron Kikinis, Fiona M Fennessy, and Clare M Tempany. 2/2020. “Open Source Platform for Transperineal In-Bore MRI-Guided Targeted Prostate Biopsy.” IEEE Trans Biomed Eng, 67, 2, Pp. 565-76.Abstract
OBJECTIVE: Accurate biopsy sampling of the suspected lesions is critical for the diagnosis and clinical management of prostate cancer. Transperineal in-bore MRI-guided prostate biopsy (tpMRgBx) is a targeted biopsy technique that was shown to be safe, efficient, and accurate. Our goal was to develop an open source software platform to support evaluation, refinement, and translation of this biopsy approach. METHODS: We developed SliceTracker, a 3D Slicer extension to support tpMRgBx. We followed modular design of the implementation to enable customization of the interface and interchange of image segmentation and registration components to assess their effect on the processing time, precision, and accuracy of the biopsy needle placement. The platform and supporting documentation were developed to enable the use of software by an operator with minimal technical training to facilitate translation. Retrospective evaluation studied registration accuracy, effect of the prostate segmentation approach, and re-identification time of biopsy targets. Prospective evaluation focused on the total procedure time and biopsy targeting error (BTE). RESULTS: Evaluation utilized data from 73 retrospective and ten prospective tpMRgBx cases. Mean landmark registration error for retrospective evaluation was 1.88 ± 2.63 mm, and was not sensitive to the approach used for prostate gland segmentation. Prospectively, we observed target re-identification time of 4.60 ± 2.40 min and BTE of 2.40 ± 0.98 mm. CONCLUSION: SliceTracker is modular and extensible open source platform for supporting image processing aspects of the tpMRgBx procedure. It has been successfully utilized to support clinical research procedures at our site.
Guoqiang Xie, Fan Zhang, Laura Leung, Michael A Mooney, Lorenz Epprecht, Isaiah Norton, Yogesh Rathi, Ron Kikinis, Ossama Al-Mefty, Nikos Makris, Alexandra J Golby, and Lauren J O'Donnell. 1/2020. “Anatomical Assessment of Trigeminal Nerve Tractography Using Diffusion MRI: A Comparison of Acquisition B-Values and Single- and Multi-Fiber Tracking Strategies.” Neuroimage Clin, 25, Pp. 102160.Abstract
BACKGROUND: The trigeminal nerve (TGN) is the largest cranial nerve and can be involved in multiple inflammatory, compressive, ischemic or other pathologies. Currently, imaging-based approaches to identify the TGN mostly rely on T2-weighted magnetic resonance imaging (MRI), which provides localization of the cisternal portion of the TGN where the contrast between nerve and cerebrospinal fluid (CSF) is high enough to allow differentiation. The course of the TGN within the brainstem as well as anterior to the cisternal portion, however, is more difficult to display on traditional imaging sequences. An advanced imaging technique, diffusion MRI (dMRI), enables tracking of the trajectory of TGN fibers and has the potential to visualize anatomical regions of the TGN not seen on T2-weighted imaging. This may allow a more comprehensive assessment of the nerve in the context of pathology. To date, most work in TGN tracking has used clinical dMRI acquisitions with a b-value of 1000 s/mm and conventional diffusion tensor MRI (DTI) tractography methods. Though higher b-value acquisitions and multi-tensor tractography methods are known to be beneficial for tracking brain white matter fiber tracts, there have been no studies conducted to evaluate the performance of these advanced approaches on nerve tracking of the TGN, in particular on tracking different anatomical regions of the TGN. OBJECTIVE: We compare TGN tracking performance using dMRI data with different b-values, in combination with both single- and multi-tensor tractography methods. Our goal is to assess the advantages and limitations of these different strategies for identifying the anatomical regions of the TGN. METHODS: We proposed seven anatomical rating criteria including true and false positive structures, and we performed an expert rating study of over 1000 TGN visualizations, as follows. We tracked the TGN using high-quality dMRI data from 100 healthy adult subjects from the Human Connectome Project (HCP). TGN tracking performance was compared across dMRI acquisitions with b = 1000 s/mm, b = 2000 s/mm and b = 3000 s/mm, using single-tensor (1T) and two-tensor (2T) unscented Kalman filter (UKF) tractography. This resulted in a total of six tracking strategies. The TGN was identified using an anatomical region-of-interest (ROI) selection approach. First, in a subset of the dataset we identified ROIs that provided good TGN tracking performance across all tracking strategies. Using these ROIs, the TGN was then tracked in all subjects using the six tracking strategies. An expert rater (GX) visually assessed and scored each TGN based on seven anatomical judgment criteria. These criteria included the presence of multiple expected anatomical segments of the TGN (true positive structures), specifically branch-like structures, cisternal portion, mesencephalic trigeminal tract, and spinal cord tract of the TGN. False positive criteria included the presence of any fibers entering the temporal lobe, the inferior cerebellar peduncle, or the middle cerebellar peduncle. Expert rating scores were analyzed to compare TGN tracking performance across the six tracking strategies. Intra- and inter-rater validation was performed to assess the reliability of the expert TGN rating result. RESULTS: The TGN was selected using two anatomical ROIs (Meckel's Cave and cisternal portion of the TGN). The two-tensor tractography method had significantly better performance on identifying true positive structures, while generating more false positive streamlines in comparison to the single-tensor tractography method. TGN tracking performance was significantly different across the three b-values for almost all structures studied. Tracking performance was reported in terms of the percentage of subjects achieving each anatomical rating criterion. Tracking of the cisternal portion and branching structure of the TGN was generally successful, with the highest performance of over 98% using two-tensor tractography and b = 1000 or b = 2000. However, tracking the smaller mesencephalic and spinal cord tracts of the TGN was quite challenging (highest performance of 37.5% and 57.07%, using two-tensor tractography with b = 1000 and b = 2000, respectively). False positive connections to the temporal lobe (over 38% of subjects for all strategies) and cerebellar peduncles (100% of subjects for all strategies) were prevalent. High joint probability of agreement was obtained in the inter-rater (on average 83%) and intra-rater validation (on average 90%), showing a highly reliable expert rating result. CONCLUSIONS: Overall, the results of the study suggest that researchers and clinicians may benefit from tailoring their acquisition and tracking methodology to the specific anatomical portion of the TGN that is of the greatest interest. For example, tracking of branching structures and TGN-T2 overlap can be best achieved with a two-tensor model and an acquisition using b = 1000 or b = 2000. In general, b = 1000 and b = 2000 acquisitions provided the best-rated tracking results. Further research is needed to improve both sensitivity and specificity of the depiction of the TGN anatomy using dMRI.
Lorenz Epprecht, Ahad Qureshi, Elliott D Kozin, Nicolas Vachicouras, Alexander M Huber, Ron Kikinis, Nikos Makris, Christian M Brown, Katherine L Reinshagen, and Daniel J Lee. 1/2020. “Human Cochlear Nucleus on 7 Tesla Diffusion Tensor Imaging: Insights Into Micro-anatomy and Function for Auditory Brainstem Implant Surgery.” Otol Neurotol.Abstract
OBJECTIVE: The cochlear nucleus (CN) is the target of the auditory brainstem implant (ABI). Most ABI candidates have Neurofibromatosis Type 2 (NF2) and distorted brainstem anatomy from bilateral vestibular schwannomas. The CN is difficult to characterize as routine structural MRI does not resolve detailed anatomy. We hypothesize that diffusion tensor imaging (DTI) enables both in vivo localization and quantitative measurements of CN morphology. STUDY DESIGN: We analyzed 7 Tesla (T) DTI images of 100 subjects (200 CN) and relevant anatomic structures using an MRI brainstem atlas with submillimetric (50 μm) resolution. SETTING: Tertiary referral center. PATIENTS: Young healthy normal hearing adults. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Diffusion scalar measures such as fractional anisotropy (FA), mean diffusivity (MD), mode of anisotropy (Mode), principal eigenvectors of the CN, and the adjacent inferior cerebellar peduncle (ICP). RESULTS: The CN had a lamellar structure and ventral-dorsal fiber orientation and could be localized lateral to the inferior cerebellar peduncle (ICP). This fiber orientation was orthogonal to tracts of the adjacent ICP where the fibers run mainly caudal-rostrally. The CN had lower FA compared to the medial aspect of the ICP (0.44 ± 0.09 vs. 0.64 ± 0.08, p < 0.001). CONCLUSIONS: 7T DTI enables characterization of human CN morphology and neuronal substructure. An ABI array insertion vector directed more caudally would better correspond to the main fiber axis of CN. State-of-the-art DTI has implications for ABI preoperative planning and future image guidance-assisted placement of the electrode array.
James J Levitt, Paul G Nestor, Marek Kubicki, Amanda E Lyall, Fan Zhang, Tammy Riklin-Raviv, Lauren J O Donnell, Robert W McCarley, Martha E Shenton, and Yogesh Rathi. 1/2020. “Miswiring of Frontostriatal Projections in Schizophrenia.” Schizophr Bull.Abstract
We investigated brain wiring in chronic schizophrenia and healthy controls in frontostriatal circuits using diffusion magnetic resonance imaging tractography in a novel way. We extracted diffusion streamlines in 27 chronic schizophrenia and 26 healthy controls connecting 4 frontal subregions to the striatum. We labeled the projection zone striatal surface voxels into 2 subtypes: dominant-input from a single cortical subregion, and, functionally integrative, with mixed-input from diverse cortical subregions. We showed: 1) a group difference for total striatal surface voxel number (P = .045) driven by fewer mixed-input voxels in the left (P  = .007), but not right, hemisphere; 2) a group by hemisphere interaction for the ratio quotient between voxel subtypes (P  = .04) with a left (P  = .006), but not right, hemisphere increase in schizophrenia, also reflecting fewer mixed-input voxels; and 3) fewer mixed-input voxel counts in schizophrenia (P  = .045) driven by differences in left hemisphere limbic (P  = .007) and associative (P  = .01), but not sensorimotor, striatum. These results demonstrate a less integrative pattern of frontostriatal structural connectivity in chronic schizophrenia. A diminished integrative pattern yields a less complex input pattern to the striatum from the cortex with less circuit integration at the level of the striatum. Further, as brain wiring occurs during early development, aberrant brain wiring could serve as a developmental biomarker for schizophrenia.
Laurent Chauvin, Kuldeep Kumar, Christian Wachinger, Marc Vangel, Jacques de Guise, Christian Desrosiers, William Wells, and Matthew Toews. 1/2020. “Neuroimage Signature from Salient Keypoints is Highly Specific to Individuals and Shared by Close Relatives.” Neuroimage, 204, Pp. 116208.Abstract
Neuroimaging studies typically adopt a common feature space for all data, which may obscure aspects of neuroanatomy only observable in subsets of a population, e.g. cortical folding patterns unique to individuals or shared by close relatives. Here, we propose to model individual variability using a distinctive keypoint signature: a set of unique, localized patterns, detected automatically in each image by a generic saliency operator. The similarity of an image pair is then quantified by the proportion of keypoints they share using a novel Jaccard-like measure of set overlap. Experiments demonstrate the keypoint method to be highly efficient and accurate, using a set of 7536 T1-weighted MRIs pooled from four public neuroimaging repositories, including twins, non-twin siblings, and 3334 unique subjects. All same-subject image pairs are identified by a similarity threshold despite confounds including aging and neurodegenerative disease progression. Outliers reveal previously unknown data labeling inconsistencies, demonstrating the usefulness of the keypoint signature as a computational tool for curating large neuroimage datasets.