Publications

2024

Costello H, Schrag AE, Howard R, Roiser JP. Dissociable effects of dopaminergic medications on depression symptom dimensions in Parkinson disease.. Nature. Mental health. 2024;2(8):916–923. PMID: 39131186

Depression in Parkinson disease (PD) is common, is disabling and responds poorly to standard antidepressants. Motivational symptoms of depression are particularly prevalent in PD and emerge with loss of dopaminergic innervation of the striatum. Optimizing dopaminergic treatment for PD can improve depressive symptoms. However, the differential effect of antiparkinsonian medication on symptom dimensions of depression is not known. Using data from a large (n = 412) longitudinal study of patients with newly diagnosed PD followed over 5 years, we investigated whether there are dissociable effects of dopaminergic medications on different depression symptom dimensions in PD. Previously validated 'motivation' and 'depression' dimensions were derived from the 15-item geriatric depression scale. Dopaminergic neurodegeneration was measured using repeated striatal dopamine transporter imaging. We identified dissociable associations between dopaminergic medications and different dimensions of depression in PD. Dopamine agonists were shown to be effective for treatment of motivational symptoms of depression. In contrast, monoamine oxidase-B inhibitors improved both depressive and motivation symptoms, albeit the latter effect is attenuated in patients with more severe striatal dopaminergic neurodegeneration.

Zhang F, Cho KIK, Seitz-Holland J, Ning L, Legarreta JH, Rathi Y, Westin CF, O’Donnell LJ, Pasternak O. DDParcel: Deep Learning Anatomical Brain Parcellation From Diffusion MRI.. IEEE transactions on medical imaging. 2024;43(3):1191–1202. PMID: 37943635

Parcellation of anatomically segregated cortical and subcortical brain regions is required in diffusion MRI (dMRI) analysis for region-specific quantification and better anatomical specificity of tractography. Most current dMRI parcellation approaches compute the parcellation from anatomical MRI (T1- or T2-weighted) data, using tools such as FreeSurfer or CAT12, and then register it to the diffusion space. However, the registration is challenging due to image distortions and low resolution of dMRI data, often resulting in mislabeling in the derived brain parcellation. Furthermore, these approaches are not applicable when anatomical MRI data is unavailable. As an alternative we developed the Deep Diffusion Parcellation (DDParcel), a deep learning method for fast and accurate parcellation of brain anatomical regions directly from dMRI data. The input to DDParcel are dMRI parameter maps and the output are labels for 101 anatomical regions corresponding to the FreeSurfer Desikan-Killiany (DK) parcellation. A multi-level fusion network leverages complementary information in the different input maps, at three network levels: input, intermediate layer, and output. DDParcel learns the registration of diffusion features to anatomical MRI from the high-quality Human Connectome Project data. Then, to predict brain parcellation for a new subject, the DDParcel network no longer requires anatomical MRI data but only the dMRI data. Comparing DDParcel's parcellation with T1w-based parcellation shows higher test-retest reproducibility and a higher regional homogeneity, while requiring much less computational time. Generalizability is demonstrated on a range of populations and dMRI acquisition protocols. Utility of DDParcel's parcellation is demonstrated on tractography analysis for fiber tract identification.

Park TY, Franke L, Pieper S, Haehn D, Ning L. A review of algorithms and software for real-time electric field modeling techniques for transcranial magnetic stimulation.. Biomedical engineering letters. 2024;14(3):393–405. PMID: 38645587

Transcranial magnetic stimulation (TMS) is a device-based neuromodulation technique increasingly used to treat brain diseases. Electric field (E-field) modeling is an important technique in several TMS clinical applications, including the precision stimulation of brain targets with accurate stimulation density for the treatment of mental disorders and the localization of brain function areas for neurosurgical planning. Classical methods for E-field modeling usually take a long computation time. Fast algorithms are usually developed with significantly lower spatial resolutions that reduce the prediction accuracy and limit their usage in real-time or near real-time TMS applications. This review paper discusses several modern algorithms for real-time or near real-time TMS E-field modeling and their advantages and limitations. The reviewed methods include techniques such as basis representation techniques and deep neural-network-based methods. This paper also provides a review of software tools that can integrate E-field modeling with navigated TMS, including a recent software for real-time navigated E-field mapping based on deep neural-network models.

Juvekar P, Dorent R, Kögl F, Torio E, Barr C, Rigolo L, Galvin C, Jowkar N, Kazi A, Haouchine N, Cheema H, Navab N, Pieper S, Wells WM, Bi WL, Golby A, Frisken S, Kapur T. ReMIND: The Brain Resection Multimodal Imaging Database.. Scientific data. 2024;11(1):494. PMID: 38744868

The standard of care for brain tumors is maximal safe surgical resection. Neuronavigation augments the surgeon's ability to achieve this but loses validity as surgery progresses due to brain shift. Moreover, gliomas are often indistinguishable from surrounding healthy brain tissue. Intraoperative magnetic resonance imaging (iMRI) and ultrasound (iUS) help visualize the tumor and brain shift. iUS is faster and easier to incorporate into surgical workflows but offers a lower contrast between tumorous and healthy tissues than iMRI. With the success of data-hungry Artificial Intelligence algorithms in medical image analysis, the benefits of sharing well-curated data cannot be overstated. To this end, we provide the largest publicly available MRI and iUS database of surgically treated brain tumors, including gliomas (n = 92), metastases (n = 11), and others (n = 11). This collection contains 369 preoperative MRI series, 320 3D iUS series, 301 iMRI series, and 356 segmentations collected from 114 consecutive patients at a single institution. This database is expected to help brain shift and image analysis research and neurosurgical training in interpreting iUS and iMRI.

Juvekar P, Dorent R, Kögl F, Torio E, Barr C, Rigolo L, Galvin C, Jowkar N, Kazi A, Haouchine N, Cheema H, Navab N, Pieper S, Wells WM, Bi WL, Golby A, Frisken S, Kapur T. ReMIND: The Brain Resection Multimodal Imaging Database.. medRxiv : the preprint server for health sciences. 2024;. PMID: 37745329

The standard of care for brain tumors is maximal safe surgical resection. Neuronavigation augments the surgeon's ability to achieve this but loses validity as surgery progresses due to brain shift. Moreover, gliomas are often indistinguishable from surrounding healthy brain tissue. Intraoperative magnetic resonance imaging (iMRI) and ultrasound (iUS) help visualize the tumor and brain shift. iUS is faster and easier to incorporate into surgical workflows but offers a lower contrast between tumorous and healthy tissues than iMRI. With the success of data-hungry Artificial Intelligence algorithms in medical image analysis, the benefits of sharing well-curated data cannot be overstated. To this end, we provide the largest publicly available MRI and iUS database of surgically treated brain tumors, including gliomas (n=92), metastases (n=11), and others (n=11). This collection contains 369 preoperative MRI series, 320 3D iUS series, 301 iMRI series, and 356 segmentations collected from 114 consecutive patients at a single institution. This database is expected to help brain shift and image analysis research and neurosurgical training in interpreting iUS and iMRI.

Pace DF, Contreras HTM, Romanowicz J, Ghelani S, Rahaman I, Zhang Y, Gao P, Jubair MI, Yeh T, Golland P, Geva T, Ghelani S, Powell AJ, Moghari MH. HVSMR-2.0: A 3D cardiovascular MR dataset for whole-heart segmentation in congenital heart disease.. Scientific data. 2024;11(1):721. PMID: 38956063

Patients with congenital heart disease often have cardiac anatomy that deviates significantly from normal, frequently requiring multiple heart surgeries. Image segmentation from a preoperative cardiovascular magnetic resonance (CMR) scan would enable creation of patient-specific 3D surface models of the heart, which have potential to improve surgical planning, enable surgical simulation, and allow automatic computation of quantitative metrics of heart function. However, there is no publicly available CMR dataset for whole-heart segmentation in patients with congenital heart disease. Here, we release the HVSMR-2.0 dataset, comprising 60 CMR scans alongside manual segmentation masks of the 4 cardiac chambers and 4 great vessels. The images showcase a wide range of heart defects and prior surgical interventions. The dataset also includes masks of required and optional extents of the great vessels, enabling fairer comparisons across algorithms. Detailed diagnoses for each subject are also provided. By releasing HVSMR-2.0, we aim to encourage development of robust segmentation algorithms and clinically relevant tools for congenital heart disease.

Tchetchenian A, Zekelman L, Chen Y, Rushmore J, Zhang F, Yeterian EH, Makris N, Rathi Y, Meijering E, Song Y, O’Donnell LJ. Deep multimodal saliency parcellation of cerebellar pathways: Linking microstructure and individual function through explainable multitask learning.. Human brain mapping. 2024;45(12):e70008. PMID: 39185598

Parcellation of human cerebellar pathways is essential for advancing our understanding of the human brain. Existing diffusion magnetic resonance imaging tractography parcellation methods have been successful in defining major cerebellar fibre tracts, while relying solely on fibre tract structure. However, each fibre tract may relay information related to multiple cognitive and motor functions of the cerebellum. Hence, it may be beneficial for parcellation to consider the potential importance of the fibre tracts for individual motor and cognitive functional performance measures. In this work, we propose a multimodal data-driven method for cerebellar pathway parcellation, which incorporates both measures of microstructure and connectivity, and measures of individual functional performance. Our method involves first training a multitask deep network to predict various cognitive and motor measures from a set of fibre tract structural features. The importance of each structural feature for predicting each functional measure is then computed, resulting in a set of structure-function saliency values that are clustered to parcellate cerebellar pathways. We refer to our method as Deep Multimodal Saliency Parcellation (DeepMSP), as it computes the saliency of structural measures for predicting cognitive and motor functional performance, with these saliencies being applied to the task of parcellation. Applying DeepMSP to a large-scale dataset from the Human Connectome Project Young Adult study (n = 1065), we found that it was feasible to identify multiple cerebellar pathway parcels with unique structure-function saliency patterns that were stable across training folds. We thoroughly experimented with all stages of the DeepMSP pipeline, including network selection, structure-function saliency representation, clustering algorithm, and cluster count. We found that a 1D convolutional neural network architecture and a transformer network architecture both performed comparably for the multitask prediction of endurance, strength, reading decoding, and vocabulary comprehension, with both architectures outperforming a fully connected network architecture. Quantitative experiments demonstrated that a proposed low-dimensional saliency representation with an explicit measure of motor versus cognitive category bias achieved the best parcellation results, while a parcel count of four was most successful according to standard cluster quality metrics. Our results suggested that motor and cognitive saliencies are distributed across the cerebellar white matter pathways. Inspection of the final k = 4 parcellation revealed that the highest-saliency parcel was most salient for the prediction of both motor and cognitive performance scores and included parts of the middle and superior cerebellar peduncles. Our proposed saliency-based parcellation framework, DeepMSP, enables multimodal, data-driven tractography parcellation. Through utilising both structural features and functional performance measures, this parcellation strategy may have the potential to enhance the study of structure-function relationships of the cerebellar pathways.

Lasič S, Chakwizira A, Lundell H, Westin CF, Nilsson M. Tuned exchange imaging: Can the filter exchange imaging pulse sequence be adapted for applications with thin slices and restricted diffusion?. NMR in biomedicine. 2024;:e5208. PMID: 38961745

Filter exchange imaging (FEXI) is a double diffusion-encoding (DDE) sequence that is specifically sensitive to exchange between sites with different apparent diffusivities. FEXI uses a diffusion-encoding filtering block followed by a detection block at varying mixing times to map the exchange rate. Long mixing times enhance the sensitivity to exchange, but they pose challenges for imaging applications that require a stimulated echo sequence with crusher gradients. Thin imaging slices require strong crushers, which can introduce significant diffusion weighting and bias exchange rate estimates. Here, we treat the crushers as an additional encoding block and consider FEXI as a triple diffusion-encoding sequence. This allows the bias to be corrected in the case of multi-Gaussian diffusion, but not easily in the presence of restricted diffusion. Our approach addresses challenges in the presence of restricted diffusion and relies on the ability to independently gauge sensitivities to exchange and restricted diffusion for arbitrary gradient waveforms. It follows two principles: (i) the effects of crushers are included in the forward model using signal cumulant expansion; and (ii) timing parameters of diffusion gradients in filter and detection blocks are adjusted to maintain the same level of restriction encoding regardless of the mixing time. This results in the tuned exchange imaging (TEXI) protocol. The accuracy of exchange mapping with TEXI was assessed through Monte Carlo simulations in spheres of identical sizes and gamma-distributed sizes, and in parallel hexagonally packed cylinders. The simulations demonstrate that TEXI provides consistent exchange rates regardless of slice thickness and restriction size, even with strong crushers. However, the accuracy depends on b-values, mixing times, and restriction geometry. The constraints and limitations of TEXI are discussed, including suggestions for protocol adaptations. Further studies are needed to optimize the precision of TEXI and assess the approach experimentally in realistic, heterogeneous substrates.

Halle MW, Kikinis R, Neumann PE. TA2Viewer: A web-based browser for Terminologia Anatomica and online anatomical knowledge.. Clinical anatomy (New York, N.Y.). 2024;37(6):640–648. PMID: 38556919

TA2Viewer is an open-access, web-based application and database for browsing anatomical terms and associated medical information on a computer or mobile device (https://ta2viewer.openanatomy.org/). It incorporates the official digital version of the second edition of Terminologia Anatomica (TA2) as published by the Federative International Programme for Anatomical Terminology (FIPAT), and adopted by the International Federation of Associations of Anatomists (IFAA) and other associations. It provides a dynamic and interactive view of the Latin and English nomenclatures. The organizational hierarchy of the terminology can be navigated by using a scrollable, expandable, and collapsible structured listing. Interactive search includes the official TA2 terms, synonyms, and related terms. TA2Viewer also uses TA2 term information to provide convenient access to other online resources, including Google web and image searches, PubMed, and Radiopaedia. Using cross-references from Wikidata, which were provided by the Wikipedia community, TA2Viewer offers links to Wikipedia, UBERON, UMLS, FMA, MeSH, NeuroNames, the public domain 20th edition of Gray's Anatomy, and other data sources. In addition, it can optionally use unofficial synonyms from Wikidata to provide multilingual term searches in hundreds of languages. By leveraging TA2, TA2Viewer provides free access to a curated anatomical nomenclature and serves as an index of online anatomical knowledge.

Epprecht L, Zekelman L, Reinshagen KL, Xie G, Norton I, Kikinis R, Makris N, Piccirelli M, Huber A, Lee DJ, Zhang F, O’Donnell LJ. Facial Nerve Tractography Using Diffusion MRI: A Comparison of Acquisition b -Values and Single- and Multifiber Tracking Strategies.. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2024;45(9):e647-e654. PMID: 39234825

HYPOTHESIS: This study investigates the impact of different diffusion magnetic imaging (dMRI) acquisition settings and mathematical fiber models on tractography performance for depicting cranial nerve (CN) VII in healthy young adults.

BACKGROUND: The aim of this study is to optimize visualization of CN VII for preoperative assessment in surgeries near the nerve in the cerebellopontine angle, reducing surgery-associated complications. The study analyzes 100 CN VII in dMRI images from the Human Connectome Project, using three separate sets with different b values ( b = 1,000 s/mm 2 , b =2,000 s/mm 2 , b =3,000 s/mm 2 ) and four different tractography methods, resulting in 1,200 tractographies analyzed.

RESULTS: The results show that multifiber and free water (FW) compartment models produce significantly more streamlines than single-fiber tractography. The addition of an FW compartment significantly increases the mean streamline fractional anisotropy (FA). Expert quality ratings showed that the highest rated tractography was the 1 tensor (1T) method without FW at b values of 1,000 s/mm2.

CONCLUSIONS: In this young and healthy cohort, best tractography results are obtained by using a 1T model without a FW compartment in b =1,000 diffusion MR images. The FW compartment increased the contrast between streamlines and cerebrospinal fluid (higher mean streamline FA). This finding may help ongoing research to improve CN VII tractography results in tumor cases where the nerve is often stretched and thinned by the tumor.