Postmortem examination of patient H.M.’s brain based on histological sectioning and digital 3D reconstruction

Modern scientific knowledge of how memory functions are organized in the human brain originated from the case of Henry G. Molaison (H.M.), an epileptic patient whose amnesia ensued unexpectedly following a bilateral surgical ablation of medial temporal lobe structures, including the hippocampus. The neuroanatomical extent of the 1953 operation could not be assessed definitively during H.M.’s life. Here we describe the results of a procedure designed to reconstruct a microscopic anatomical model of the whole brain and conduct detailed 3D measurements in the medial temporal lobe region. This approach, combined with cellular-level imaging of stained histological slices, demonstrates a significant amount of residual hippocampal tissue with distinctive cytoarchitecture. Our study also reveals diffuse pathology in the deep white matter and a small, circumscribed lesion in the left orbitofrontal cortex. The findings constitute new evidence that may help elucidate the consequences of H.M.’s operation in the context of the brain’s overall pathology

Voxel Level Radiologic-Pathologic Validation of Restriction Spectrum Imaging Cellularity Index with Gleason Grade in Prostate Cancer.

PurposeRestriction spectrum imaging (RSI-MRI), an advanced diffusion imaging technique, can potentially circumvent current limitations in tumor conspicuity, in vivo characterization, and location demonstrated by multiparametric magnetic resonance imaging (MP-MRI) techniques in prostate cancer detection. Prior reports show that the quantitative signal derived from RSI-MRI, the cellularity index, is associated with aggressive prostate cancer as measured by Gleason grade (GG). We evaluated the reliability of RSI-MRI to predict variance with GG at the voxel-level within clinically demarcated prostate cancer regions.Experimental designTen cases were processed using whole mount sectioning after radical prostatectomy. Regions of tumor were identified by an uropathologist. Stained prostate sections were scanned at high resolution (75 μm/pixel). A grid of tiles corresponding to voxel dimensions was graded using the GG system. RSI-MRI cellularity index was calculated from presurgical prostate MR scans and presented as normalized z-score maps. In total, 2,795 tiles were analyzed and compared with RSI-MRI cellularity.ResultsRSI-MRI cellularity index was found to distinguish between prostate cancer and benign tumor (t = 25.48, P < 0.00001). Significant differences were also found between benign tissue and prostate cancer classified as low-grade (GG = 3; t = 11.56, P < 0.001) or high-grade (GG ≥ 4; t = 24.03, P < 0.001). Furthermore, RSI-MRI differentiated between low and high-grade prostate cancer (t = 3.23; P = 0.003).ConclusionsBuilding on our previous findings of correlation between GG and the RSI-MRI among whole tumors, our current study reveals a similar correlation at voxel resolution within tumors. Because it can detect variations in tumor grade with voxel-level precision, RSI-MRI may become an option for planning targeted procedures where identifying the area with the most aggressive disease is important. Clin Cancer Res; 22(11); 2668-74. ©2016 AACR

Demonstration of non-gaussian restricted diffusion in tumor cells using diffusion time-dependent diffusion-weighted magnetic resonance imaging contrast

The diffusion-weighted magnetic resonance imaging (DWI) technique enables quantification of water mobility for probing microstructural properties of biological tissue and has become an effective tool for collecting information about the underlying pathology of cancerous tissue. Measurements using multiple b-values have indicated biexponential signal attenuation, ascribed to “fast” (high ADC) and “slow” (low ADC) diffusion components. In this empirical study, we investigate the properties of the diffusion time (Δ)-dependent components of the diffusion-weighted (DW) signal in a constant b-value experiment. A xenograft gliobastoma mouse was imaged using Δ = 11 ms, 20 ms, 40 ms, 60 ms, and b = 500–4000 s/mm2 in intervals of 500 s/mm2. Data were corrected for EPI distortions, and the Δ-dependence on the DW-signal was measured within three regions of interest [intermediate- and high-density tumor regions and normal-appearing brain (NAB) tissue regions]. In this study, we verify the assumption that the slow decaying component of the DW-signal is non-Gaussian and dependent on Δ, consistent with restricted diffusion of the intracellular space. As the DW-signal is a function of Δ and is specific to restricted diffusion, manipulating Δ at constant b-value (cb) provides a complementary and direct approach for separating the restricted from the hindered diffusion component. We found that Δ-dependence is specific to the tumor tissue signal. Based on an extended biexponential model, we verified the interpretation of the diffusion time-dependent contrast and successfully estimated the intracellular restricted ADC, signal volume fraction, and cell size within each ROI

Demonstration of Non-Gaussian Restricted Diffusion in Tumor Cells Using Diffusion Time-Dependent Diffusion-Weighted Magnetic Resonance Imaging Contrast

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Demonstration of Non-Gaussian Restricted Diffusion in Tumor Cells Using Diffusion Time-Dependent Diffusion-Weighted Magnetic Resonance Imaging Contrast.

The diffusion-weighted magnetic resonance imaging (DWI) technique enables quantification of water mobility for probing microstructural properties of biological tissue and has become an effective tool for collecting information about the underlying pathology of cancerous tissue. Measurements using multiple b-values have indicated biexponential signal attenuation, ascribed to "fast" (high ADC) and "slow" (low ADC) diffusion components. In this empirical study, we investigate the properties of the diffusion time (Δ)-dependent components of the diffusion-weighted (DW) signal in a constant b-value experiment. A xenograft gliobastoma mouse was imaged using Δ = 11 ms, 20 ms, 40 ms, 60 ms, and b = 500-4000 s/mm(2) in intervals of 500 s/mm(2). Data were corrected for EPI distortions, and the Δ-dependence on the DW-signal was measured within three regions of interest [intermediate- and high-density tumor regions and normal-appearing brain (NAB) tissue regions]. In this study, we verify the assumption that the slow decaying component of the DW-signal is non-Gaussian and dependent on Δ, consistent with restricted diffusion of the intracellular space. As the DW-signal is a function of Δ and is specific to restricted diffusion, manipulating Δ at constant b-value (cb) provides a complementary and direct approach for separating the restricted from the hindered diffusion component. We found that Δ-dependence is specific to the tumor tissue signal. Based on an extended biexponential model, we verified the interpretation of the diffusion time-dependent contrast and successfully estimated the intracellular restricted ADC, signal volume fraction, and cell size within each ROI

Demonstration of non-gaussian restricted diffusion in tumor cells using diffusion time-dependent diffusion-weighted magnetic resonance imaging contrast

The diffusion-weighted magnetic resonance imaging (DWI) technique enables quantification of water mobility for probing microstructural properties of biological tissue and has become an effective tool for collecting information about the underlying pathology of cancerous tissue. Measurements using multiple b-values have indicated biexponential signal attenuation, ascribed to “fast” (high ADC) and “slow” (low ADC) diffusion components. In this empirical study, we investigate the properties of the diffusion time (Δ)-dependent components of the diffusion-weighted (DW) signal in a constant b-value experiment. A xenograft gliobastoma mouse was imaged using Δ = 11 ms, 20 ms, 40 ms, 60 ms, and b = 500–4000 s/mm2 in intervals of 500 s/mm2. Data were corrected for EPI distortions, and the Δ-dependence on the DW-signal was measured within three regions of interest [intermediate- and high-density tumor regions and normal-appearing brain (NAB) tissue regions]. In this study, we verify the assumption that the slow decaying component of the DW-signal is non-Gaussian and dependent on Δ, consistent with restricted diffusion of the intracellular space. As the DW-signal is a function of Δ and is specific to restricted diffusion, manipulating Δ at constant b-value (cb) provides a complementary and direct approach for separating the restricted from the hindered diffusion component. We found that Δ-dependence is specific to the tumor tissue signal. Based on an extended biexponential model, we verified the interpretation of the diffusion time-dependent contrast and successfully estimated the intracellular restricted ADC, signal volume fraction, and cell size within each ROI

Prostate diffusion imaging with distortion correction.

PurposeDiffusion imaging in the prostate is susceptible to distortion from B0 inhomogeneity. Distortion correction in prostate imaging is not routinely performed, resulting in diffusion images without accurate localization of tumors. We performed and evaluated distortion correction for diffusion imaging in the prostate.Materials and methods28 patients underwent pre-operative MRI (T2, Gadolinium perfusion, diffusion at b=800 s/mm(2)). The restriction spectrum protocol parameters included b-values of 0, 800, 1500, and 4000 s/mm(2) in 30 directions for each nonzero b-value. To correct for distortion, forward and reverse trajectories were collected at b=0 s/mm(2). Distortion maps were generated to reflect the offset of the collected data versus the corrected data. Whole-mount histology was available for correlation.ResultsAcross the 27 patients evaluated (excluding one patient due to data collection error), the average root mean square distortion distance of the prostate was 3.1 mm (standard deviation, 2.2mm; and maximum distortion, 12 mm).ConclusionImproved localization of prostate cancer by MRI will allow better surgical planning, targeted biopsies and image-guided treatment therapies. Distortion distances of up to 12 mm due to standard diffusion imaging may grossly misdirect treatment decisions. Distortion correction for diffusion imaging in the prostate improves tumor localization

Restriction spectrum imaging: An evolving imaging biomarker in prostate MRI.

Restriction spectrum imaging (RSI) is a novel diffusion-weighted MRI technique that uses the mathematically distinct behavior of water diffusion in separable microscopic tissue compartments to highlight key aspects of the tissue microarchitecture with high conspicuity. RSI can be acquired in less than 5 min on modern scanners using a surface coil. Multiple field gradients and high b-values in combination with postprocessing techniques allow the simultaneous resolution of length-scale and geometric information, as well as compartmental and nuclear volume fraction filtering. RSI also uses a distortion correction technique and can thus be fused to high resolution T2-weighted images for detailed localization, which improves delineation of disease extension into critical anatomic structures. In this review, we discuss the acquisition, postprocessing, and interpretation of RSI for prostate MRI. We also summarize existing data demonstrating the applicability of RSI for prostate cancer detection, in vivo characterization, localization, and targeting.Level of evidence5 J. Magn. Reson. Imaging 2017;45:323-336

Restriction spectrum imaging improves MRI-based prostate cancer detection.

PurposeTo compare the diagnostic performance of restriction spectrum imaging (RSI), with that of conventional multi-parametric (MP) magnetic resonance imaging (MRI) for prostate cancer (PCa) detection in a blinded reader-based format.MethodsThree readers independently evaluated 100 patients (67 with proven PCa) who underwent MP-MRI and RSI within 6 months of systematic biopsy (N = 67; 23 with targeting performed) or prostatectomy (N = 33). Imaging was performed at 3 Tesla using a phased-array coil. Readers used a five-point scale estimating the likelihood of PCa present in each prostate sextant. Evaluation was performed in two separate sessions, first using conventional MP-MRI alone then immediately with MP-MRI and RSI in the same session. Four weeks later, another scoring session used RSI and T2-weighted imaging (T2WI) without conventional diffusion-weighted or dynamic contrast-enhanced imaging. Reader interpretations were then compared to prostatectomy data or biopsy results. Receiver operating characteristic curves were performed, with area under the curve (AUC) used to compare across groups.ResultsMP-MRI with RSI achieved higher AUCs compared to MP-MRI alone for identifying high-grade (Gleason score greater than or equal to 4 + 3=7) PCa (0.78 vs. 0.70 at the sextant level; P < 0.001 and 0.85 vs. 0.79 at the hemigland level; P = 0.04). RSI and T2WI alone achieved AUCs similar to MP-MRI for high-grade PCa (0.71 vs. 0.70 at the sextant level). With hemigland analysis, high-grade disease results were similar when comparing RSI + T2WI with MP-MRI, although with greater AUCs compared to the sextant analysis (0.80 vs. 0.79).ConclusionIncluding RSI with MP-MRI improves PCa detection compared to MP-MRI alone, and RSI with T2WI achieves similar PCa detection as MP-MRI