Samantha Malowane Leventis
Masters Student in Computer Science, admitted Autumn 2022
All Publications
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Precise MRI-histology coregistration of paraffin-embedded tissue with blockface imaging.
Imaging neuroscience (Cambridge, Mass.)
2025; 3
Abstract
Magnetic resonance imaging (MRI) provides 3D spatial information on tissue, yet it lacks at the molecular level. In contrast, histology provides cellular and molecular information, but it lacks the 3D spatial context and direct in vivo translation. Coregistering the two is key for the 3D embedding of histological details, validating pathological MRI findings, and identifying quantitative imaging biomarkers of neurodegenerative diseases. However, coregistration is challenging due to non-linear distortions of the tissue from histological processing and sectioning leading to microscopic and macroscopic nonlinear 3D deformations between specimen MRI and stained histology sections. To address this, we developed a novel pipeline, named Brewster's Blockface Quantification (BBQ), integrating robust optical approaches with innovative 2D and 3D registration algorithms to achieve precise volumetric alignment of specimen MRI data with histological images. On a variety of brain tissue specimens from distinct anatomical regions and across multiple species, our methodology generated blockface volumes with minimal distortion and artifacts. Using these blockface volumes as an intermediary, we achieve a precise alignment between MRI and histology slides, yielding registration results with an overlapping Dice score of ~90% for whole tissue alignment between MRI and blockface volumes, and >95% for 2D MRI-histology registration. This correlative MRI-histology pipeline with robust 2D and 3D coregistration methods promises to enhance our understanding of neurodegenerative diseases and aid the development of MRI-based disease biomarkers.
View details for DOI 10.1162/IMAG.a.106
View details for PubMedID 40800888
View details for PubMedCentralID PMC12336061
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Precise MRI-Histology Coregistration of Paraffin-Embedded Tissue with Blockface Imaging.
bioRxiv : the preprint server for biology
2025
Abstract
Magnetic resonance imaging (MRI) provides 3D spatial information on tissue, yet it lacks at the molecular level. In contrast, histology provides cellular and molecular information, but it lacks the 3D spatial context and direct in vivo translation. Coregistering the two is key for the 3D-embedding of histological details, validating pathological MRI findings, and finding quantitative imaging biomarkers of neurodegenerative diseases. However, coregistration is challenging due to non-linear distortions of the tissue from histological processing and sectioning leading to microscopic and macroscopic nonlinear 3D deformations between specimen MRI and stained histology sections. To address this, we developed a novel pipeline, named Brewster's Blockface Quantification (BBQ), integrating robust optical approaches with innovative 2D and 3D registration algorithms to achieve precise volumetric alignment of specimen MRI data with histological images. On a variety of brain tissue specimens from distinct anatomical regions and across multiple species, our methodology generated blockface volumes with minimal distortion and artifacts. Using these blockface volumes as an intermediary, we achieve a precise alignment between MRI and histology slides, yielding registration results with an overlapping Dice score of ~90% for whole tissue alignment between MRI and blockface volumes, and >95% for 2D MRI-histology registration. This correlative MRI-histology pipeline with robust 2D and 3D coregistration methods promises to enhance our understanding of neurodegenerative diseases and aid the development of MRI-based disease biomarkers.
View details for DOI 10.1101/2025.06.02.657335
View details for PubMedID 40501733
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Clinical Manifestations.
Alzheimer's & dementia : the journal of the Alzheimer's Association
2024; 20 Suppl 3: e092936
Abstract
Olfactory deficiency can be present in preclinical Alzheimer's (AD) and Parkinson's disease (PD), predicting their subsequent manifestation, including mild cognitive impairment (MCI). Analyzing key regions within the olfactory circuit could reveal important insights into the neuropathological progression. Dysfunction in the olfactory circuit has been shown in the olfactory nerve in limited postmortem studies, including involvement of a key region, the piriform cortex. FDG-positron emission tomography (PET) and fMRI have shown differential and reduced piriform cortex metabolism/activation in AD. Thus, the piriform cortex is a promising candidate in the early identification of neurodegenerative pathology underlying olfaction. We used tau MR-PET to analyze the piriform cortex, in comparison to the adjacent medial temporal lobe.We analyzed 115 subjects: 23 were excluded (incomplete data), leaving 31 amyloid-negative and 25 amyloid-positive healthy controls, 8 MCI, 15 AD, and 13 PD. All subjects underwent MR-PET using tau tracer PI-2620 with a simultaneous coregistered sagittal T1-weighted 3D IR-FSPGR and a simultaneous/recently acquired coronal T2-weighted FSE. Automatic Segmentation of Hippocampal Subfields was performed, including the entorhinal-perirhinal cortices (Fig. 1D-F). Referencing published piriform segmentation guidelines, we manually segmented blind to subject diagnosis the frontal/temporal portions of the piriform cortex (Fig. 1C), including multiple independent quality control checks. As tau distributions appeared non-normal among the five ordinal patient categories (Amyloid-HC, Amyloid+HC, MCI, AD, Normal PD), we used a nonparametric Jonckheere-Terpstra test in Stata to test for ordinal increase in tau uptake across four regions bilaterally (whole hippocampus = CA1-4 + DG + subiculum, entorhinal-perirhinal, amygdala, and piriform).We found an ordinal increase in piriform tau uptake with increasing disease severity (amyloid-negative controls, amyloid-positive controls, MCI and AD) (Figure 2A-D). Amyloid-positive controls showed significantly greater uptake than amyloid-negative controls. Piriform uptake was not elevated in cognitively unimpaired PD compared to Amyloid-HC. Piriform volume was statistically equivalent across groups, except PD had lower volumes (Figure 2E-H). Negative correlations were present between memory performance and piriform uptake (Figure 3).Cross-sectionally, there is an early increase in tau uptake in the piriform cortex in AD but not in PD.
View details for DOI 10.1002/alz.092936
View details for PubMedID 39750218
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Biomarkers.
Alzheimer's & dementia : the journal of the Alzheimer's Association
2024; 20 Suppl 2: e092110
Abstract
MRI offers potential noninvasive detection of Alzheimer's micropathology. The AD hippocampus exhibits microscopic pathological changes such as tau tangles, iron accumulation and late-stage amyloid. Validating these changes from ultra-high-resolution ex-vivo MRI through histology is challenging due to nonlinear 3D deformations between MRI and histological samples. We aim to address the challenge by a pipeline (Figure 1) for precise alignment of post-mortem MRI data with histological images.A human hippocampal specimen was dissected from a formalin-fixed human brain and divided into hippocampal head and tail. We obtained high-resolution multi-echo gradient echo ex vivo MRI of each using a 7T Bruker scanner. The specimens were paraffin-embedded and sectioned using a Leica Histocore Nanocut R microtome. An optical image of the tissue block's surface was captured before each section was cut (Blockface image) using a polarized filter at Brewster's angle. The obtained 2D blockface images were aligned and filtered into 3D blockface volumes. These were registered with MRI using either Tensor Image Registration Library (TIRL) with Modality Independent Neighbourhood Descriptor, or ANTs SyN registration. Subsequently, the 2D MRI slices corresponding to the stained histology slides were identified in the 3D volume and underwent 2D deformable registration with TIRL or ANTs. To quantify the registration accuracy, we segmented hippocampal volumes into white matter, grey matter, and dentate gyrus for MRI, blockface, and histology data separately.When comparing 3D MR and blockface 3D image segmentations (Figure 2, top), the average Dice similarity coefficient of hippocampal head and tail were 86.2% and 86.76% with TIRL, and 83.91% and 78.26% with ANTs SyN. Evaluating 2D MR registration to histological images, TIRL achieves the average Dice coefficient of 94.12% and 96.95%. ANTs performs marginally better across the whole tissue mask, but TIRL shows superior performance in the internal features (Table 1). High-fidelity alignment shows very small features such as focal hypointensities (Figure 2, bottom, blue circles) and the dentate granule cell layer (orange arrows).Our advanced correlative MRI-histology pipeline achieves micron-level precision coregistration methods at micron-scale precision, propelling the development of MRI-based AD biomarkers.
View details for DOI 10.1002/alz.092110
View details for PubMedID 39785486
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Elevated tau in the piriform cortex in Alzheimer's but not Parkinson's disease using PET-MR.
Alzheimer's & dementia (Amsterdam, Netherlands)
2024; 16 (4): e70040
Abstract
Olfactory dysfunction can be an early sign of Alzheimer's disease (AD). We used tau positron emission tomography-magnetic resonance (PET-MR) to analyze a key region of the olfactory circuit, the piriform cortex, in comparison to the adjacent medial temporal lobe.Using co-registered magnetic resonance imaging (MRI) and 18F-PI-2620 tau PET-MR scans in 94 older adults, we computed tau uptake in the piriform-periamygdaloid cortex, amygdala, entorhinal-perirhinal cortices, and hippocampus.We found an ordinal cross-sectional increase in piriform cortex tau uptake with increasing disease severity (amyloid-negative controls, amyloid-positive controls, mild cognitive impairment [MCI] and AD), comparable to entorhinal-perirhinal cortex. Amyloid-positive controls showed significantly greater tau uptake than amyloid-negative controls. Negative correlations were present between memory performance and piriform uptake. Piriform uptake was not elevated in cognitively unimpaired Parkinson's disease.Cross-sectionally, there is an early increase in tau uptake in the piriform cortex in AD but not in Parkinson's disease.Positron emission tomography-magnetic resonance (PET-MR) analysis of the piriform cortex sheds light on its role as a potential early region affected by neurodegenerative disorders underlying olfactory dysfunction.Uptake of tau tracer was elevated in the piriform cortex in Alzheimer's disease (AD) and mild cognitive impairment (MCI) but not in Parkinson's disease (PD).Memory performance was worse with greater piriform uptake.
View details for DOI 10.1002/dad2.70040
View details for PubMedID 39583648
View details for PubMedCentralID PMC11585164