Abulnaga M, Turk EA, Bessmeltsev M, Grant E, Solomon J, Golland P. Volumetric Parameterization of the Placenta to a Flattened Template. IEEE Trans Med Imaging 2022;41(4):925-36.

We present a volumetric mesh-based algorithm for parameterizing the placenta to a flattened template to enable effective visualization of local anatomy and function. MRI shows potential as a research tool as it provides signals directly related to placental function. However, due to the curved and highly variable in vivo shape of the placenta, interpreting and visualizing these images is difficult. We address interpretation challenges by mapping the placenta so that it resembles the familiar ex vivo shape. We formulate the parameterization as an optimization problem for mapping the placental shape represented by a volumetric mesh to a flattened template. We employ the symmetric Dirichlet energy to control local distortion throughout the volume. Local injectivity in the mapping is enforced by a constrained line search during the gradient descent optimization. We validate our method using a research study of 111 placental shapes extracted from BOLD MRI images. Our mapping achieves sub-voxel accuracy in matching the template while maintaining low distortion throughout the volume. We demonstrate how the resulting flattening of the placenta improves visualization of anatomy and function. Our code is freely available at

Seitz-Holland J, Seethaler M, Makris N, Rushmore J, Cho K-IK, Rizzoni E, Vangel M, Sahin OS, Heller C, Pasternak O, Szczepankiewicz F, Westin C-F, Lošák J, Ustohal L, Tomandl J, Vojtíšek L, Kudlička P, Jáni M, Woo W, Kašpárek T, Kikinis Z, Kubicki M. The Association of Matrix Metalloproteinase 9 (MMP9) With Hippocampal Volume in Schizophrenia: A Preliminary MRI Study. Neuropsychopharmacology 2022;47(2):524-30.

Matrix metalloproteinases 9 (MMP9) are enzymes involved in regulating neuroplasticity in the hippocampus. This, combined with evidence for disrupted hippocampal structure and function in schizophrenia, has prompted our current investigation into the relationship between MMP9 and hippocampal volumes in schizophrenia. 34 healthy individuals (mean age = 32.50, male = 21, female = 13) and 30 subjects with schizophrenia (mean age = 33.07, male = 19, female = 11) underwent a blood draw and T1-weighted magnetic resonance imaging. The hippocampus was automatically segmented utilizing FreeSurfer. MMP9 plasma levels were measured with ELISA. ANCOVAs were conducted to compare MMP9 plasma levels (corrected for age and sex) and hippocampal volumes between groups (corrected for age, sex, total intracranial volume). Spearman correlations were utilized to investigate the relationship between symptoms, medication, duration of illness, number of episodes, and MMP9 plasma levels in patients. Last, we explored the correlation between MMP9 levels and hippocampal volumes in patients and healthy individuals separately. Patients displayed higher MMP9 plasma levels than healthy individuals (F(1, 60) = 21.19, p < 0.0001). MMP9 levels correlated with negative symptoms in patients (R = 0.39, p = 0.035), but not with medication, duration of illness, or the number of episodes. Further, patients had smaller left (F(1,59) = 9.12, p = 0.0040) and right (F(1,59) = 6.49, p = 0.013) hippocampal volumes. Finally, left (R = -0.39, p = 0.034) and right (R = -0.37, p = 0.046) hippocampal volumes correlated negatively with MMP9 plasma levels in patients. We observe higher MMP9 plasma levels in SCZ, associated with lower hippocampal volumes, suggesting involvement of MMP9 in the pathology of SCZ. Future studies are needed to investigate how MMP9 influences the pathology of SCZ over the lifespan, whether the observed associations are specific for schizophrenia, and if a therapeutic modulation of MMP9 promotes neuroprotective effects in SCZ.

Chauvin L, Kumar K, Desrosiers C, Wells W, Toews M. Efficient Pairwise Neuroimage Analysis Using the Soft Jaccard Index and 3D Keypoint Sets. IEEE Trans Med Imaging 2022;41(4):836-45.

We propose a novel pairwise distance measure between image keypoint sets, for the purpose of large-scale medical image indexing. Our measure generalizes the Jaccard index to account for soft set equivalence (SSE) between keypoint elements, via an adaptive kernel framework modeling uncertainty in keypoint appearance and geometry. A new kernel is proposed to quantify the variability of keypoint geometry in location and scale. Our distance measure may be estimated between O (N 2) image pairs in [Formula: see text] operations via keypoint indexing. Experiments report the first results for the task of predicting family relationships from medical images, using 1010 T1-weighted MRI brain volumes of 434 families including monozygotic and dizygotic twins, siblings and half-siblings sharing 100%-25% of their polymorphic genes. Soft set equivalence and the keypoint geometry kernel improve upon standard hard set equivalence (HSE) and appearance kernels alone in predicting family relationships. Monozygotic twin identification is near 100%, and three subjects with uncertain genotyping are automatically paired with their self-reported families, the first reported practical application of image-based family identification. Our distance measure can also be used to predict group categories, sex is predicted with an AUC = 0.97. Software is provided for efficient fine-grained curation of large, generic image datasets.

Pace DF, Dalca A, Brosch T, Geva T, Powell AJ, Weese J, Moghari MH, Golland P. Learned Iterative Segmentation of Highly Variable Anatomy From Limited Data: Applications to Whole Heart Segmentation for Congenital Heart Disease. Med Image Anal 2022;80:102469.

Training deep learning models that segment an image in one step typically requires a large collection of manually annotated images that captures the anatomical variability in a cohort. This poses challenges when anatomical variability is extreme but training data is limited, as when segmenting cardiac structures in patients with congenital heart disease (CHD). In this paper, we propose an iterative segmentation model and show that it can be accurately learned from a small dataset. Implemented as a recurrent neural network, the model evolves a segmentation over multiple steps, from a single user click until reaching an automatically determined stopping point. We develop a novel loss function that evaluates the entire sequence of output segmentations, and use it to learn model parameters. Segmentations evolve predictably according to growth dynamics encapsulated by training data, which consists of images, partially completed segmentations, and the recommended next step. The user can easily refine the final segmentation by examining those that are earlier or later in the output sequence. Using a dataset of 3D cardiac MR scans from patients with a wide range of CHD types, we show that our iterative model offers better generalization to patients with the most severe heart malformations.

Taymourtash A, Schwartz E, Nenning K-H, Sobotka D, Licandro R, Glatter S, Diogo MC, Golland P, Grant E, Prayer D, Kasprian G, Langs G. Fetal Development of Functional Thalamocortical and Cortico-Cortical Connectivity. Cereb Cortex 2022;(9):5613-24.

Measuring and understanding functional fetal brain development in utero is critical for the study of the developmental foundations of our cognitive abilities, possible early detection of disorders, and their prevention. Thalamocortical connections are an intricate component of shaping the cortical layout, but so far, only ex-vivo studies provide evidence of how axons enter the sub-plate and cortex during this highly dynamic phase. Evidence for normal in-utero development of the functional thalamocortical connectome in humans is missing. Here, we modeled fetal functional thalamocortical connectome development using in-utero functional magnetic resonance imaging in fetuses observed from 19th to 40th weeks of gestation (GW). We observed a peak increase of thalamocortical functional connectivity strength between 29th and 31st GW, right before axons establish synapses in the cortex. The cortico-cortical connectivity increases in a similar time window, and exhibits significant functional laterality in temporal-superior, -medial, and -inferior areas. Homologous regions exhibit overall similar mirrored connectivity profiles, but this similarity decreases during gestation giving way to a more diverse cortical interconnectedness. Our results complement the understanding of structural development of the human connectome and may serve as the basis for the investigation of disease and deviations from a normal developmental trajectory of connectivity development.

Yu Y, Bourantas G, Zwick B, Joldes G, Kapur T, Frisken S, Kikinis R, Nabavi A, Golby A, Wittek A, Miller K. Computer Simulation of Tumour Resection-Induced Brain Deformation by a Meshless Approach. Int J Numer Method Biomed Eng 2022;38(1):e3539.
Tumour resection requires precise planning and navigation to maximise tumour removal while simultaneously protecting nearby healthy tissues. Neurosurgeons need to know the location of the remaining tumour after partial tumour removal before continuing with the resection. Our approach to the problem uses biomechanical modelling and computer simulation to compute the brain deformations after the tumour is resected. In this study, we use meshless Total Lagrangian explicit dynamics as the solver. The problem geometry is extracted from the patient-specific magnetic resonance imaging (MRI) data and includes the parenchyma, tumour, cerebrospinal fluid and skull. The appropriate non-linear material formulation is used. Loading is performed by imposing intra-operative conditions of gravity and reaction forces between the tumour and surrounding healthy parenchyma tissues. A finite frictionless sliding contact is enforced between the skull (rigid) and parenchyma. The meshless simulation results are compared to intra-operative MRI sections. We also calculate Hausdorff distances between the computed deformed surfaces (ventricles and tumour cavities) and surfaces observed intra-operatively. Over 80% of points on the ventricle surface and 95% of points on the tumour cavity surface were successfully registered (results within the limits of two times the original in-plane resolution of the intra-operative image). Computed results demonstrate the potential for our method in estimating the tissue deformation and tumour boundary during the resection.
Maier-Hein L, Eisenmann M, Sarikaya D, März K, Collins T, Malpani A, Fallert J, Feussner H, Giannarou S, Mascagni P, Nakawala H, Park A, Pugh C, Stoyanov D, Vedula SS, Cleary K, Fichtinger G, Forestier G, Gibaud B, Grantcharov T, Hashizume M, Heckmann-Nötzel D, Kenngott HG, Kikinis R, Mündermann L, Navab N, Onogur S, Roß T, Sznitman R, Taylor RH, Tizabi MD, Wagner M, Hager GD, Neumuth T, Padoy N, Collins J, Gockel I, Goedeke J, Hashimoto DA, Joyeux L, Lam K, Leff DR, Madani A, Marcus HJ, Meireles O, Seitel A, Teber D, Ückert F, Müller-Stich BP, Jannin P, Speidel S. Surgical Data Science - From Concepts Toward Clinical Translation. Med Image Anal 2022;76:102306.
Recent developments in data science in general and machine learning in particular have transformed the way experts envision the future of surgery. Surgical Data Science (SDS) is a new research field that aims to improve the quality of interventional healthcare through the capture, organization, analysis and modeling of data. While an increasing number of data-driven approaches and clinical applications have been studied in the fields of radiological and clinical data science, translational success stories are still lacking in surgery. In this publication, we shed light on the underlying reasons and provide a roadmap for future advances in the field. Based on an international workshop involving leading researchers in the field of SDS, we review current practice, key achievements and initiatives as well as available standards and tools for a number of topics relevant to the field, namely (1) infrastructure for data acquisition, storage and access in the presence of regulatory constraints, (2) data annotation and sharing and (3) data analytics. We further complement this technical perspective with (4) a review of currently available SDS products and the translational progress from academia and (5) a roadmap for faster clinical translation and exploitation of the full potential of SDS, based on an international multi-round Delphi process.
Guttuso T, Sirica D, Tosun D, Zivadinov R, Pasternak O, Weintraub D, Baglio F, Bergsland N. Thalamic Dorsomedial Nucleus Free Water Correlates with Cognitive Decline in Parkinson’s Disease. Mov Disord 2022;37(3):490-501.
BACKGROUND: Brain diffusion tensor imaging (DTI) has been shown to reflect cognitive changes in early Parkinson s disease (PD) but the diffusion-based measure free water (FW) has not been previously assessed. OBJECTIVES: To assess if FW in the thalamic nuclei primarily involved with cognition (ie, the dorsomedial [DMN] and anterior [AN] nuclei), the nucleus basalis of Meynert (nbM), and the hippocampus correlates with and is associated with longitudinal cognitive decline and distinguishes cognitive status at baseline in early PD. Also, to explore how FW compares with conventional DTI, FW-corrected DTI, and volumetric assessments for these outcomes. METHODS: Imaging data and Montreal Cognitive Assessment (MoCA) scores from the Parkinson’s Progression Markers Initiative database were analyzed using partial correlations and ANCOVA. Primary outcome multiple comparisons were corrected for false discovery rate (q value). RESULTS: Thalamic DMN FW changes over 1 year correlated with MoCA changes over both 1 and 3 years (partial correlations -0.222, q = 0.040, n = 130; and - 0.229, q = 0.040, n = 123, respectively; mean PD duration at baseline = 6.85 months). NbM FW changes over 1 year only correlated with MoCA changes over 3 years (-0.222, q = 0.040). Baseline hippocampal FW was associated with cognitive impairment at 3 years (q = 0.040) and baseline nbM FW distinguished PD-normal cognition (MoCA >=26) from PD-cognitive impairment (MoCA
Zaks N, Velikonja T, Parvaz MA, Zinberg J, Done M, Mathalon DH, Addington J, Cadenhead K, Cannon T, Cornblatt B, McGlashan T, Perkins D, Stone WS, Tsuang M, Walker E, Woods SW, Keshavan MS, Buysse DJ, Velthorst E, Bearden CE. Sleep Disturbance in Individuals at Clinical High Risk for Psychosis. Schizophr Bull 2022;48(1):111-21.
INTRODUCTION: Disturbed sleep is a common feature of psychotic disorders that is also present in the clinical high risk (CHR) state. Evidence suggests a potential role of sleep disturbance in symptom progression, yet the interrelationship between sleep and CHR symptoms remains to be determined. To address this knowledge gap, we examined the association between disturbed sleep and CHR symptoms over time. METHODS: Data were obtained from the North American Prodrome Longitudinal Study (NAPLS)-3 consortium, including 688 CHR individuals and 94 controls (mean age 18.25, 46% female) for whom sleep was tracked prospectively for 8 months. We used Cox regression analyses to investigate whether sleep disturbances predicted conversion to psychosis up to >2 years later. With regressions and cross-lagged panel models, we analyzed longitudinal and bidirectional associations between sleep (the Pittsburgh Sleep Quality Index in conjunction with additional sleep items) and CHR symptoms. We also investigated the independent contribution of individual sleep characteristics on CHR symptom domains separately and explored whether cognitive impairments, stress, depression, and psychotropic medication affected the associations. RESULTS: Disturbed sleep at baseline did not predict conversion to psychosis. However, sleep disturbance was strongly correlated with heightened CHR symptoms over time. Depression accounted for half of the association between sleep and symptoms. Importantly, sleep was a significant predictor of CHR symptoms but not vice versa, although bidirectional effect sizes were similar. DISCUSSION: The critical role of sleep disturbance in CHR symptom changes suggests that sleep may be a promising intervention target to moderate outcome in the CHR state.
Bayat A, Pace DF, Sekuboyina A, Payer C, Stern D, Urschler M, Kirschke JS, Menze BH. Anatomy-Aware Inference of the 3D Standing Spine Posture from 2D Radiographs. Tomography 2022;8(1):479-96.
An important factor for the development of spinal degeneration, pain and the outcome of spinal surgery is known to be the balance of the spine. It must be analyzed in an upright, standing position to ensure physiological loading conditions and visualize load-dependent deformations. Despite the complex 3D shape of the spine, this analysis is currently performed using 2D radiographs, as all frequently used 3D imaging techniques require the patient to be scanned in a prone position. To overcome this limitation, we propose a deep neural network to reconstruct the 3D spinal pose in an upright standing position, loaded naturally. Specifically, we propose a novel neural network architecture, which takes orthogonal 2D radiographs and infers the spine’s 3D posture using vertebral shape priors. In this work, we define vertebral shape priors using an atlas and a spine shape prior, incorporating both into our proposed network architecture. We validate our architecture on digitally reconstructed radiographs, achieving a 3D reconstruction Dice of 0.95, indicating an almost perfect 2D-to-3D domain translation. Validating the reconstruction accuracy of a 3D standing spine on real data is infeasible due to the lack of a valid ground truth. Hence, we design a novel experiment for this purpose, using an orientation invariant distance metric, to evaluate our model’s ability to synthesize full-3D, upright, and patient-specific spine models. We compare the synthesized spine shapes from clinical upright standing radiographs to the same patient’s 3D spinal posture in the prone position from CT.