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Previous methods used to infer axon diameter distributions using magnetic resonance imaging (MRI) primarily use single diffusion encoding sequences such as pulsed gradient spin echo (PGSE) and are thus sensitive to axons of diameters >5 μm. We applied oscillating gradient spin echo (OGSE) sequences to study human axons in the 1-2 μm range in the corpus callosum, which include the majority of axons constituting cortical connections. The ActiveAx model was applied to calculate the fitted mean effective diameter for axons (AxD) and was compared with values found using histology. Axon diameters from histological data were calculated using three different datasets; true diameters (minimum diameter), a combination of minimum and maximum diameters, and diameters measured across a consistent diffusion direction. The AxD estimates from MRI were 1.8 ± 0.1 μm to 2.34 ± 0.04 μm with an average of 2.0 ± 0.2 μm for the ActiveAx model. The histology AxD values were 1.43 ± 0.02 μm when using the true minimum axon diameters, 5.52 ± 0.02 μm when using the combination of minimum and maximum axon diameters, and 2.20 ± 0.02 μm when collecting measurements across a consistent diffusion direction. This experiment demonstrates the first known usage of OGSE to calculate axon diameters in the human corpus callosum on a 1-2 μm scale. The importance for the model to account for axonal orientation dispersion is indicated by histological results which more closely match the MRI model results depending on the direction of axon diameter measurements. These initial steps using this non-invasive imaging method can be applied to future methodology to develop in vivo axon diameter measurements in human brain tissue., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The establishment of whole-slide imaging (WSI) as a medical diagnostic device allows that pathologists may evaluate mitotic activity with this new technology. Furthermore, the image digitalization provides an opportunity to develop algorithms for automatic quantifications, ideally leading to improved reproducibility as compared to the naked eye examination by pathologists. In order to implement them effectively, accuracy of mitotic figure detection using WSI should be investigated. In this study, we aimed to measure pathologist performance in detecting mitotic figures (MFs) using multiple platforms (multiple scanners) and compare the results with those obtained using a brightfield microscope., Methods: Four slides of canine oral melanoma were prepared and digitized using 4 WSI scanners. In these slides, 40 regions of interest (ROIs) were demarcated, and five observers identified the MFs using different viewing modes: microscopy and WSI. We evaluated the inter- and intra-observer agreements between modes with Cohen's Kappa and determined "true" MFs with a consensus panel. We then assessed the accuracy (agreement with truth) using the average of sensitivity and specificity., Results: In the 40 ROIs, 155 candidate MFs were detected by five pathologists; 74 of them were determined to be true MFs. Inter- and intra-observer agreement was mostly "substantial" or greater (Kappa = 0.594-0.939). Accuracy was between 0.632 and 0.843 across all readers and modes. After averaging over readers for each modality, we found that mitosis detection accuracy for 3 of the 4 WSI scanners was significantly less than that of the microscope (p = 0.002, 0.012, and 0.001)., Conclusions: This study is the first to compare WSIs and microscopy in detecting MFs at the level of individual cells. Our results suggest that WSI can be used for mitotic cell detection and offers similar reproducibility to the microscope, with slightly less accuracy.

Purpose: Postmortem MRI can be used to reveal important pathologies and establish radiology-pathology correlations. However, quantitative MRI values are altered by tissue fixation. Therefore, the purpose of this study was to investigate time-dependent effects of formalin fixation on MRI relaxometry (T 1 and T 2 ), diffusion tensor imaging (fractional anisotropy, FA; and mean diffusivity, MD), and myelin water fraction (MWF) measurements throughout intact human brain specimens., Methods: Two whole, neurologically-healthy human brains were immersed in 10% formalin solution and scanned at 13 time points between 0 and 1,032 h. Whole-brain maps of longitudinal (T 1 ) and transverse (T 2 ) relaxation times, FA, MD, and MWF were generated at each time point to illustrate spatiotemporal changes, and region-of-interest analyses were then performed in eight brain structures to quantify temporal changes with progressive fixation., Results: Although neither of the diffusion measures (FA nor MD) showed significant changes as a function of formalin fixation time, both T 1 and T 2 -relaxation times significantly decreased, and MWF estimates significantly increased with progressive fixation until (and likely beyond) our final measurements were taken at 1,032 h., Conclusion: These results suggest that T 1 -relaxation, T 2 -relaxation and MWF estimates must be performed quite early in the fixation process to avoid formalin-induced changes compared to in vivo values; and furthermore, that different ex vivo scans within an experiment must be acquired at consistent (albeit still early) fixation intervals to avoid fixative-related differences between samples. Conversely, ex vivo diffusion measures (FA and MD) appear to depend more on other factors (e.g., pulse sequence optimization, sample temperature, etc.).

To advance magnetic resonance imaging (MRI) technologies further for in vivo tissue characterization with histopathologic validation, we investigated the feasibility of ex vivo tissue imaging of a surgically removed human brain tumor as a comprehensive approach for radiology-pathology correlation in histoanatomically identical fashion in a rare case of pigmented ganglioglioma with complex paramagnetic properties. Pieces of surgically removed ganglioglioma, containing melanin and hemosiderin pigments, were imaged with a small bore 7-T MRI scanner to obtain T1-, T2-, and T2*-weighted image and diffusion tensor imaging (DTI). Corresponding histopathological slides were prepared for routine hematoxylin and eosin stain and special stains for melanin and iron/hemosiderin to correlate with MRI signal characteristics. Furthermore, mean diffusivity (MD) maps were generated from DTI data and correlated with cellularity using image analysis. While the presence of melanin was difficult to interpret in in vivo MRI with certainty due to concomitant hemosiderin pigments and calcium depositions, ex vivo tissue imaging clearly demonstrated pieces of tissue exhibiting the characteristic MR signal pattern for melanin with pathologic confirmation in a histoanatomically identical location. There was also concordant correlation between MD and cellularity. Although it is still in an initial phase of development, ex vivo tissue imaging is a promising approach, which offers radiology-pathology correlation in a straightforward and comprehensive manner.

Magnetic resonance imaging (MRI) is a non-destructive technique that is capable of localizing pathologies and assessing other anatomical features (e.g., tissue volume, microstructure, and white matter connectivity) in postmortem, ex vivo human brains. However, when brains are removed from the skull and cerebrospinal fluid (i.e., their normal in vivo magnetic environment), air bubbles and air-tissue interfaces typically cause magnetic susceptibility artifacts that severely degrade the quality of ex vivo MRI data. In this report, we describe a relatively simple and cost-effective experimental setup for acquiring artifact-free ex vivo brain images using a clinical MRI system with standard hardware. In particular, we outline the necessary steps, from collecting an ex vivo human brain to the MRI scanner setup, and have also described changing the formalin (as might be necessary in longitudinal postmortem studies). Finally, we share some representative ex vivo MRI images that have been acquired using the proposed setup in order to demonstrate the efficacy of this approach. We hope that this protocol will provide both clinicians and researchers with a straight-forward and cost-effective solution for acquiring ex vivo MRI data from whole postmortem human brains.

Purpose: To evaluate the feasibility of using strain-encoded (SENC) breast magnetic resonance images (MRI) for breast cancer detection by examining the compression and relaxation response properties in phantoms and ex vivo breast samples., Methods: A tissue phantom was constructed to mimic different sizes of breast masses and tissue stiffness. In addition, five human ex vivo whole breast specimens with and without masses were studied. MR data was acquired on a 3T scanner consisting of T(1)-weighted, fat suppressed spin echo T(2)-weighted, and SENC breast images. Mechanical tissue characteristics (strain) of the phantoms and breast tissue samples were measured using SENC imaging in both compression and relaxation modes. The breast tissue specimens were sectioned and stained in the same plane as the MRI for histological evaluation., Results: For the phantom, SENC images showed soft masses with quantitative strain values between 35% and 50%, while harder masses had strain values between 0% and 20%. Combined compression (CMP) and relaxation (REX) breast SENC images separately categorized all masses into three different groups. For breast SENC, the signal intensities between ex vivo breast mass and breast glandular tissue were significantly different (-7.6 ± 2.6 verses -20.6 ± 5.4 for SENC-CMP, and 4.2 ± 1.5 verses 22.6 ± 5 for SENC-REX, p < 0.05)., Conclusions: We have demonstrated that SENC breast MRI can be used to obtain mechanical tissue properties and give quantitative estimates of strain in tumors. This feasibility study provides the basis for future clinical studies.

We present the cytological features along with histologic and imaging findings of a melanocytic bronchopulmonary carcinoid tumor in a patient with multiple endocrine neoplasia syndrome type 1 (MEN-1). Intraoperative touch preparations of the lung tumor showed single spindle cells and loosely cohesive aggregates of spindle cells with oval to elongated nuclei, "salt and pepper" chromatin pattern and inconspicuous nucleoli. The spindle cells occasionally contained cytoplasmic pigment, which revealed to be melanin by Fontana Masson stain on permanent processed material. Immunohistochemical stains for both synaptophysin and chromogranin were strongly positive in the spindle cells. The findings were consistent with melanocytic bronchopulmonary carcinoid tumor, which is relatively uncommon in MEN-1., (Copyright 2009 Wiley-Liss, Inc.)

In the functional proteome era, the proteomic profiling of clinicopathologic-annotated tissues is an essential step for mining and evaluating candidate biomarkers for disease. For many diseases, but especially cancer, the development of predictive biomarkers requires performing assays directly on the diseased tissue. The last decade has seen the explosion of both prognostic and predictive biomarkers in the research setting but few of these biomarkers have entered widespread clinical use. Previously, application of routine proteomic methodologies to clinical formalin-fixed and paraffin-embedded tissue specimens has provided unsatisfactory results. In this paper, we will discuss recent advancements in proteomic profiling technology for clinical applications. These approaches focus on the retention of histomorphologic information as an element of the proteomic analysis.

Pediatric neuroradiology is a fascinating and challenging field because there are normal changes associated with normal development and unique and unusual pathologies that occur in this population. The numerous new MR techniques first applied in the adult population are appropriate for use in the pediatric population, often with minimal modification of parameters. These new techniques will undoubtedly contribute significantly to use of pediatric neuroimaging, but the adult experience is not always directly transferable. The pediatric brain, particularly the immature brain is different in structure, has predilection for different types of disease processes, and may react differently to insults than the adult brain. As a result, the role of these techniques needs to be evaluated in the context of the pediatric brain and common pediatric disease processes.