Publications

2023

Zanao TA, Seitz-Holland J, O’Donnell LJ, Zhang F, Rathi Y, Lopes TM, Pimentel-Silva LR, Yassuda CL, Makris N, Shenton ME, Bouix S, Lyall AE, Cendes F. Hippocampal Sclerosis on White Matter Tracts and Memory in Individuals With Mesial Temporal Lobe Epilepsy. Epilepsia open. 2023;8(3):1111–1122.

OBJECTIVE: To investigate how the presence/side of hippocampal sclerosis (HS) are related to the white matter structure of cingulum bundle (CB), arcuate fasciculus (AF), and inferior longitudinal fasciculus (ILF) in mesial temporal lobe epilepsy (MTLE).

METHODS: We acquired diffusion-weighted magnetic resonance imaging (MRI) from 86 healthy and 71 individuals with MTLE (22 righ-HS; right-HS, 34 left-HS; left-HS, and 15 nonlesional MTLE). We utilized two-tensor tractography and fiber clustering to compare fractional anisotropy (FA) of each side/tract between groups. Additionally, we examined the association between FA and nonverbal (WMS-R) and verbal (WMS-R, RAVLT codification) memory performance for MTLE individuals.

RESULTS: White matter abnormalities depended on the side and presence of HS. The left-HS demonstrated widespread abnormalities for all tracts, the right-HS showed lower FA for ipsilateral tracts and the nonlesional MTLE group did not differ from healthy individuals. Results indicate no differences in verbal/nonverbal memory performance between the groups, but trend-level associations between higher FA of visual memory and the left CB (r = 0.286, P = 0.018), verbal memory (RAVLT) and -left CB (r = 0.335, P = 0.005), -right CB (r = 0.286, P = 0.016), and -left AF (r = 0.287, P = 0.017).

SIGNIFICANCE: Our results highlight that the presence and side of HS are crucial to understand the pathophysiology of MTLE. Specifically, left-sided HS seems to be related to widespread bilateral white matter abnormalities. Future longitudinal studies should focus on developing diagnostic and treatment strategies dependent on HS's presence/side.

Costello H, Schrag AE, Howard R, Roiser JP. Dissociable Effects of Dopaminergic Medications on Depression Symptom Dimensions in Parkinson’s Disease. medRxiv : the preprint server for health sciences. 2023;.

BACKGROUND: Depression in Parkinson's disease (PD) is common, disabling and responds poorly to standard antidepressant medication. Motivational symptoms of depression, such as apathy and anhedonia, are particularly prevalent in depression in PD and predict poor response to antidepressant treatment. Loss of dopaminergic innervation of the striatum is associated with emergence of motivational symptoms in PD, and mood fluctuations correlate with dopamine availability. Accordingly, optimising dopaminergic treatment for PD can improve depressive symptoms, and dopamine agonists have shown promising effects in improving apathy. However, the differential effect of antiparkinsonian medication on symptom dimensions of depression is not known.

AIMS: We hypothesised that there would be dissociable effects of dopaminergic medications on different depression symptom dimensions. We predicted that dopaminergic medication would specifically improve motivational symptoms, but not other symptoms, of depression. We also hypothesised that antidepressant effects of dopaminergic medications with mechanisms of action reliant on pre-synaptic dopamine neuron integrity would attenuate as pre-synaptic dopaminergic neurodegeneration progresses.

METHODS: We analysed data from a longitudinal study of 412 newly diagnosed PD patients followed over five years in the Parkinson's Progression Markers Initiative cohort. Medication state for individual classes of Parkinson's medications was recorded annually. Previously validated "motivation" and "depression" dimensions were derived from the 15-item geriatric depression scale. Dopaminergic neurodegeneration was measured using repeated striatal dopamine transporter (DAT) imaging.

RESULTS: Linear mixed-effects modelling was performed across all simultaneously acquired data points. Dopamine agonist use was associated with relatively fewer motivation symptoms as time progressed (interaction: β=-0.07, 95%CI [-0.13,-0.01], p=0.015) but had no effect on the depression symptom dimension (p=0.6). In contrast, monoamine oxidase-B (MAO-B) inhibitor use was associated with relatively fewer depression symptoms across all years (β=-0.41, 95%CI [-0.81,-0.01], p=0.047). No associations were observed between either depression or motivation symptoms and levodopa or amantadine use. There was a significant interaction between striatal DAT binding and MAO-B inhibitor use on motivation symptoms: MAO-B inhibitor use was associated with lower motivation symptoms in patients with higher striatal DAT binding (interaction: β=-0.24, 95%CI [-0.43,-0.05], p=0.012). No other medication effects were moderated by striatal DAT binding measures.

CONCLUSIONS: We identified dissociable associations between dopaminergic medications and different dimensions of depression in PD. Dopamine agonists may be effective for treatment of motivational symptoms of depression. In contrast, MAO-B inhibitors may improve both depressive and motivation symptoms, albeit the latter effect appears to be attenuated in patients with more severe striatal dopaminergic neurodegeneration, which may be a consequence of dependence on pre-synaptic dopaminergic neuron integrity.

Nejatbakhsh A, Dey N, Venkatachalam V, Yemini E, Paninski L, Varol E. Learning Probabilistic Piecewise Rigid Atlases of Model Organisms via Generative Deep Networks. Information processing in medical imaging : proceedings of the . conference. 2023;13939:332–343.

Atlases are crucial to imaging statistics as they enable the standardization of inter-subject and inter-population analyses. While existing atlas estimation methods based on fluid/elastic/diffusion registration yield high-quality results for the human brain, these deformation models do not extend to a variety of other challenging areas of neuroscience such as the anatomy of C. elegans worms and fruit flies. To this end, this work presents a general probabilistic deep network-based framework for atlas estimation and registration which can flexibly incorporate various deformation models and levels of keypoint supervision that can be applied to a wide class of model organisms. Of particular relevance, it also develops a deformable piecewise rigid atlas model which is regularized to preserve inter-observation distances between neighbors. These modeling considerations are shown to improve atlas construction and key-point alignment across a diversity of datasets with small sample sizes including neuron positions in C. elegans hermaphrodites, fluorescence microscopy of male C. elegans, and images of fruit fly wings. Code is accessible at https://github.com/amin-nejat/Deformable-Atlas.

Groves LA, Keita M, Talla S, Kikinis R, Fichtinger G, Mousavi P, Camara M. A Review of Low-cost Ultrasound Compatible Phantoms. IEEE Transactions on Biomedical Engineering. 2023;:1–12.

Ultrasound-compatible phantoms are used to develop novel US-based systems and train simulated medical interventions. The price difference between lab-made and commercially available ultrasound-compatible phantoms lead to the publication of many papers categorized as low-cost in the literature. The aim of this review was to improve the phantom selection process by summarizing the pertinent literature. We compiled papers on US-compatible spine, prostate, vascular, breast, kidney, and li ver phantoms. We reviewed papers for cost and accessibility, providing an overview of the materials, construction time, shelf life, needle insertion limits, and manufacturing and evaluation methods. This information was summarized by anatomy. The clinical application associated with each phantom was also reported for those interested in a particular intervention. Techniques and common practices for building low-cost phantoms were provided. Overall, this paper aims to summarize a breadth of ultrasound-compatible phantom research to enable informed phantom methods selection.

Xu J, Moyer D, Gagoski B, Iglesias JE, Grant E, Golland P, Adalsteinsson E. NeSVoR: Implicit Neural Representation for Slice-to-Volume Reconstruction in MRI. IEEE transactions on medical imaging. 2023;42(6):1707–1719.

Reconstructing 3D MR volumes from multiple motion-corrupted stacks of 2D slices has shown promise in imaging of moving subjects, e. g., fetal MRI. However, existing slice-to-volume reconstruction methods are time-consuming, especially when a high-resolution volume is desired. Moreover, they are still vulnerable to severe subject motion and when image artifacts are present in acquired slices. In this work, we present NeSVoR, a resolution-agnostic slice-to-volume reconstruction method, which models the underlying volume as a continuous function of spatial coordinates with implicit neural representation. To improve robustness to subject motion and other image artifacts, we adopt a continuous and comprehensive slice acquisition model that takes into account rigid inter-slice motion, point spread function, and bias fields. NeSVoR also estimates pixel-wise and slice-wise variances of image noise and enables removal of outliers during reconstruction and visualization of uncertainty. Extensive experiments are performed on both simulated and in vivo data to evaluate the proposed method. Results show that NeSVoR achieves state-of-the-art reconstruction quality while providing two to ten-fold acceleration in reconstruction times over the state-of-the-art algorithms.

Brabec J, Friedjungová M, Vašata D, Englund E, Bengzon J, Knutsson L, Szczepankiewicz F, van Westen D, Sundgren PC, Nilsson M. Meningioma Microstructure Assessed by Diffusion MRI: An Investigation of the Source of Mean Diffusivity and Fractional Anisotropy by Quantitative Histology. NeuroImage Clin. 2023;37:103365.

BACKGROUND: Mean diffusivity (MD) and fractional anisotropy (FA) from diffusion MRI (dMRI) have been associated with cell density and tissue anisotropy across tumors, but it is unknown whether these associations persist at the microscopic level.

PURPOSE: To quantify the degree to which cell density and anisotropy, as determined from histology, account for the intra-tumor variability of MD and FA in meningioma tumors. Furthermore, to clarify whether other histological features account for additional intra-tumor variability of dMRI parameters.

MATERIALS AND METHODS: We performed ex-vivo dMRI at 200 μm isotropic resolution and histological imaging of 16 excised meningioma tumor samples. Diffusion tensor imaging (DTI) was used to map MD and FA, as well as the in-plane FA (FAIP). Histology images were analyzed in terms of cell nuclei density (CD) and structure anisotropy (SA; obtained from structure tensor analysis) and were used separately in a regression analysis to predict MD and FAIP, respectively. A convolutional neural network (CNN) was also trained to predict the dMRI parameters from histology patches. The association between MRI and histology was analyzed in terms of out-of-sample (R2OS) on the intra-tumor level and within-sample R2 across tumors. Regions where the dMRI parameters were poorly predicted from histology were analyzed to identify features apart from CD and SA that could influence MD and FAIP, respectively.

RESULTS: Cell density assessed by histology poorly explained intra-tumor variability of MD at the mesoscopic level (200 μm), as median R2OS = 0.04 (interquartile range 0.01-0.26). Structure anisotropy explained more of the variation in FAIP (median R2OS = 0.31, 0.20-0.42). Samples with low R2OS for FAIP exhibited low variations throughout the samples and thus low explainable variability, however, this was not the case for MD. Across tumors, CD and SA were clearly associated with MD (R2 = 0.60) and FAIP (R2 = 0.81), respectively. In 37% of the samples (6 out of 16), cell density did not explain intra-tumor variability of MD when compared to the degree explained by the CNN. Tumor vascularization, psammoma bodies, microcysts, and tissue cohesivity were associated with bias in MD prediction based solely on CD. Our results support that FAIP is high in the presence of elongated and aligned cell structures, but low otherwise.

CONCLUSION: Cell density and structure anisotropy account for variability in MD and FAIP across tumors but cell density does not explain MD variations within the tumor, which means that low or high values of MD locally may not always reflect high or low tumor cell density. Features beyond cell density need to be considered when interpreting MD.

Hoffmann M, Singh NM, Dalca A V, Fischl B, Frost R. Can we predict motion artifacts in clinical MRI before the scan completes?. Proceedings of the International Society for Magnetic Resonance in Medicine . Scientific Meeting and Exhibition. International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition. 2023;2023.

Subject motion can cause artifacts in clinical MRI, frequently necessitating repeat scans. We propose to alleviate this inefficiency by predicting artifact scores from partial multi-shot multi-slice acquisitions, which may guide the operator in aborting corrupted scans early.

Nejatbakhsh A, Dey N, Venkatachalam V, Yemini E, Paninski L, Varol E. Learning Probabilistic Piecewise Rigid Atlases of Model Organisms via Generative Deep Networks. Information processing in medical imaging : proceedings of the . conference. 2023;13939:332–343.

Atlases are crucial to imaging statistics as they enable the standardization of inter-subject and inter-population analyses. While existing atlas estimation methods based on fluid/elastic/diffusion registration yield high-quality results for the human brain, these deformation models do not extend to a variety of other challenging areas of neuroscience such as the anatomy of C. elegans worms and fruit flies. To this end, this work presents a general probabilistic deep network-based framework for atlas estimation and registration which can flexibly incorporate various deformation models and levels of keypoint supervision that can be applied to a wide class of model organisms. Of particular relevance, it also develops a deformable piecewise rigid atlas model which is regularized to preserve inter-observation distances between neighbors. These modeling considerations are shown to improve atlas construction and key-point alignment across a diversity of datasets with small sample sizes including neuron positions in C. elegans hermaphrodites, fluorescence microscopy of male C. elegans, and images of fruit fly wings. Code is accessible at https://github.com/amin-nejat/Deformable-Atlas.

Nejatbakhsh A, Dey N, Venkatachalam V, Yemini E, Paninski L, Varol E. Learning Probabilistic Piecewise Rigid Atlases of Model Organisms via Generative Deep Networks. Information processing in medical imaging : proceedings of the . conference. 2023;13939:332–343.

Atlases are crucial to imaging statistics as they enable the standardization of inter-subject and inter-population analyses. While existing atlas estimation methods based on fluid/elastic/diffusion registration yield high-quality results for the human brain, these deformation models do not extend to a variety of other challenging areas of neuroscience such as the anatomy of C. elegans worms and fruit flies. To this end, this work presents a general probabilistic deep network-based framework for atlas estimation and registration which can flexibly incorporate various deformation models and levels of keypoint supervision that can be applied to a wide class of model organisms. Of particular relevance, it also develops a deformable piecewise rigid atlas model which is regularized to preserve inter-observation distances between neighbors. These modeling considerations are shown to improve atlas construction and key-point alignment across a diversity of datasets with small sample sizes including neuron positions in C. elegans hermaphrodites, fluorescence microscopy of male C. elegans, and images of fruit fly wings. Code is accessible at https://github.com/amin-nejat/Deformable-Atlas.

Bumm R, Zaffino P, Lasso A, Estepar RSJ, Pieper S, Wasserthal J, Spadea MF, Latshang T, Kawel-Böhm N, Wäckerlin A, Werner R, Hässig G, Furrer M, Kikinis R. From Voxels to Prognosis: AI-Driven Quantitative Chest CT Analysis Forecasts ICU Requirements in 78 COVID-19 Cases. Research square. 2023;.

BACKGROUND: The aim of the current study was to investigate the distribution and extent of lung involvement in patients with COVID-19 with AI-supported, automated computer analysis and to assess the relationship between lung involvement and the need for intensive care unit (ICU) admission. A secondary aim was to compare the performance of computer analysis with the judgment of radiological experts.

METHODS: A total of 81 patients from an open-source COVID database with confirmed COVID-19 infection were included in the study. Three patients were excluded. Lung involvement was assessed in 78 patients using computed tomography (CT) scans, and the extent of infiltration and collapse was quantified across various lung lobes and regions. The associations between lung involvement and ICU admission were analyzed. Additionally, the computer analysis of COVID-19 involvement was compared against a human rating provided by radiological experts.

RESULTS: The results showed a higher degree of infiltration and collapse in the lower lobes compared to the upper lobes (p < 0.05) No significant difference was detected in the COVID-19-related involvement of the left and right lower lobes. The right middle lobe demonstrated lower involvement compared to the right lower lobes (p < 0.05). When examining the regions, significantly more COVID-19 involvement was found when comparing the posterior vs. the anterior halves of the lungs and the lower vs. the upper half of the lungs. Patients, who required ICU admission during their treatment exhibited significantly higher COVID-19 involvement in their lung parenchyma according to computer analysis, compared to patients who remained in general wards. Patients with more than 40% COVID-19 involvement were almost exclusively treated in intensive care. A high correlation was observed between computer detection of COVID-19 affections and expert rating by radiological experts.

CONCLUSION: The findings suggest that the extent of lung involvement, particularly in the lower lobes, dorsal lungs, and lower half of the lungs, may be associated with the need for ICU admission in patients with COVID-19. Computer analysis showed a high correlation with expert rating, highlighting its potential utility in clinical settings for assessing lung involvement. This information may help guide clinical decision-making and resource allocation during ongoing or future pandemics. Further studies with larger sample sizes are warranted to validate these findings.