Postmortem Magnetic Resonance Imaging to Guide the Pathologic Cut

Absinta, Martina; Nair, Govind; Filippi, Massimo; Ray‐Chaudhury, Abhik; Reyes‐Mantilla, Maria; Pardo, Carlos A.; Reich, Daniel S.

doi:10.1097/nen.0000000000000096

Cited by 61 publications

(47 citation statements)

References 26 publications

(23 reference statements)

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“…Although the detection of cortical cerebral microinfarcts could be improved using postmortem 7 T MRI, artefacts still caused false positive results and some histologically verified microinfarcts remained undetectable in MRI scans even upon re-evaluation of the images [46,49]. Currently it is unknown whether these cortical cerebral microinfarcts escaped detection and produced false negative results in MRI scans due to problems associated with technical limitations in image resolution at 7 T or MRI-histological matching [1,37], or whether there is a subset of microinfarcts that produces a different MRI signal pattern.…”

Section: Introductionmentioning

confidence: 99%

Histological correlates of postmortem ultra-high-resolution single-section MRI in cortical cerebral microinfarcts

Yilmazer-Hanke

Mayer

Müller³

et al. 2020

acta neuropathol commun

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The identification of cerebral microinfarctions with magnetic resonance imaging (MRI) and histological methods remains challenging in aging and dementia. Here, we matched pathological changes in the microvasculature of cortical cerebral microinfarcts to MRI signals using single 100 μm-thick histological sections scanned with ultra-highresolution 11.7 T MRI. Histologically, microinfarcts were located in superficial or deep cortical layers or transcortically, compatible with the pattern of layer-specific arteriolar blood supply of the cerebral cortex. Contrary to acute microinfarcts, at chronic stages the core region of microinfarcts showed pallor with extracellular accumulation of lipofuscin and depletion of neurons, a dense meshwork of collagen 4-positive microvessels with numerous string vessels, CD68-positive macrophages and glial fibrillary acidic protein (GFAP)-positive astrocytes. In MRI scans, cortical microinfarcts at chronic stages, called chronic cortical microinfarcts here, gave hypointense signals in T1-weighted and hyperintense signals in T2-weighted images when thinning of the tissue and cavitation and/or prominent iron accumulation were present. Iron accumulation in chronic microinfarcts, histologically verified with Prussian blue staining, also produced strong hypointense T2*-weighted signals. In summary, the microinfarct core was occupied by a dense microvascular meshwork with string vessels, which was invaded by macrophages and astroglia and contained various degrees of iron accumulation. While postmortem ultra-high-resolution single-section imaging improved MRI-histological matching and the structural characterization of chronic cortical cerebral microinfarcts, miniscule microinfarcts without thinning or iron accumulation could not be detected with certainty in the MRI scans. Moreover, string vessels at the infarct margin indicate disturbances in the microcirculation in and around microinfarcts, which might be exploitable in the diagnostics of cortical cerebral microinfarcts with MRI in vivo.

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Section: Introductionmentioning

confidence: 99%

Histological correlates of postmortem ultra-high-resolution single-section MRI in cortical cerebral microinfarcts

Yilmazer-Hanke

Mayer

Müller³

et al. 2020

acta neuropathol commun

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“…Second, because the workflow is a two dimensional registration, any correlation analysis that uses our technique is limited to in plane histological features. When considering three dimensional histology to MRI registration, parameters such as inter-slice sampling interval and tissue sectioning thickness would need to be optimized (Absinta et al, 2014; Breen et al, 2005b; Goubran et al, 2013; Zarow et al, 2004) because of rapid changes in tissue architecture between slices. At high spatial resolutions and small slice thicknesses, validation of three dimensional histological registration could then be performed using three dimensional structure tensor analysis (Schilling et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Quantitative validation of a nonlinear histology-MRI coregistration method using generalized Q-sampling imaging in complex human cortical white matter

et al. 2017

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Advanced diffusion MRI methods have recently been proposed for detection of pathologies such as traumatic axonal injury and chronic traumatic encephalopathy which commonly affect complex cortical brain regions. However, radiological-pathological correlations in human brain tissue that detail the relationship between the multi-component diffusion signal and underlying pathology are lacking. We present a nonlinear voxel based two dimensional coregistration method that is useful for matching diffusion signals to quantitative metrics of high resolution histological images. When validated in ex vivo human cortical tissue at a 250 × 250 × 500 micron spatial resolution, the method proved robust in correlations between generalized q-sampling imaging and histologically based white matter fiber orientations, with r = 0.94 for the primary fiber direction and r = 0.88 for secondary fiber direction in each voxel. Importantly, however, the correlation was substantially worse with reduced spatial resolution or with fiber orientations derived using a diffusion tensor model. Furthermore, we have detailed a quantitative histological metric of white matter fiber integrity termed power coherence capable of distinguishing between architecturally complex but intact white matter from disrupted white matter regions. These methods may allow for more sensitive and specific radiological-pathological correlations of neurodegenerative diseases affecting complex gray and white matter.

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“…However, applying a similar technique to much larger brains of human or higher primates results in its own unique set of challenges. Indeed, our laboratory has published a separate paper about using a 3D-printed cutting box to align ex vivo MRI and histology in a conceptually similar manner (Absinta et al 2014). …”

Section: Discussionmentioning

confidence: 99%

“…This strategy would eliminate issues related to data registration failures in the MRI to histology matching, and additionally, would be insensitive to the presence of artifacts in either dataset. Our laboratory developed a method to help resolve the pathological data mismatch with the use of 3D-printed custom-fit cutting boxes to assist in the sectioning of human brains (Absinta et al 2014). This approach enabled high quality matching of histologic images of the gyrencephalic brains to MRI without the use of whole-brain sectioning or computational approaches and greatly eased the localization of focal areas of interest in histology using the MRI.…”

Section: Introductionmentioning

confidence: 99%

Custom fit 3D-printed brain holders for comparison of histology with MRI in marmosets

Guy

Sati

Leibovitch

et al. 2016

Journal of Neuroscience Methods

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Background MRI has the advantage of sampling large areas of tissue and locating areas of interest in 3D space in both living and ex vivo systems, whereas histology has the ability to examine thin slices of ex vivo tissue with high detail and specificity. Although both are valuable tools, it is currently difficult to make high-precision comparisons between MRI and histology due to large differences inherent to the techniques. A method combining the advantages would be an asset to understanding the pathological correlates of MRI. New Method 3D-printed brain holders were used to maintain marmoset brains in the same orientation during acquisition of ex vivo MRI and pathologic cutting of the tissue. Results The results of maintaining this same orientation show that sub-millimeter, discrete neuropathological features in marmoset brain consistently share size, shape, and location between histology and ex vivo MRI, which facilitates comparison with serial imaging acquired in vivo. Comparison with Existing Methods Existing methods use computational approaches sensitive to data input in order to warp histologic images to match large-scale features on MRI, but the new method requires no warping of images, due to a preregistration accomplished in the technique, and is insensitive to data formatting and artifacts in both MRI and histology. Conclusions The simple method of using 3D-printed brain holders to match brain orientation during pathologic sectioning and MRI acquisition enables rapid and precise comparison of small features seen on MRI to their underlying histology.

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Postmortem Magnetic Resonance Imaging to Guide the Pathologic Cut

Cited by 61 publications

References 26 publications

Histological correlates of postmortem ultra-high-resolution single-section MRI in cortical cerebral microinfarcts

Histological correlates of postmortem ultra-high-resolution single-section MRI in cortical cerebral microinfarcts

Quantitative validation of a nonlinear histology-MRI coregistration method using generalized Q-sampling imaging in complex human cortical white matter

Custom fit 3D-printed brain holders for comparison of histology with MRI in marmosets

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