David Minkoff

A high-resolution computational atlas of the human hippocampus from postmortem magnetic resonance imaging at 9.4 T

This paper describes the construction of a computational anatomical atlas of the human hippocampus. The atlas is derived from high-resolution 9.4 Tesla MRI of postmortem samples. The main subfields of the hippocampus (cornu ammonis fields CA1, CA2/3; the dentate gyrus; and the vestigial hippocampal sulcus) are labeled in the images manually using a combination of distinguishable image features and geometrical features. A synthetic average image is derived from the MRI of the samples using shape and intensity averaging in the diffeomorphic non-linear registration framework, and a consensus labeling of the template is generated. The agreement of the consensus labeling with manual labeling of each sample is measured, and the effect of aiding registration with landmarks and manually generated mask images is evaluated. The atlas is provided as an online resource with the aim of supporting subfield segmentation in emerging hippocampus imaging and image analysis techniques. An example application examining subfield-level hippocampal atrophy in temporal lobe epilepsy demonstrates the application of the atlas to in vivo studies.

Optical Bedside Monitoring of Cerebral Blood Flow in Acute Ischemic Stroke Patients During Head-of-Bed Manipulation

Background and Purpose— A primary goal of acute ischemic stroke (AIS) management is to maximize perfusion in the affected region and surrounding ischemic penumbra. However, interventions to maximize perfusion, such as flat head-of-bed (HOB) positioning, are currently prescribed empirically. Bedside monitoring of cerebral blood flow (CBF) allows the effects of interventions such as flat HOB to be monitored and may ultimately be used to guide clinical management. Methods— Cerebral perfusion was measured during HOB manipulations in 17 patients with unilateral AIS affecting large cortical territories in the anterior circulation. Simultaneous measurements of frontal CBF and arterial flow velocity were performed with diffuse correlation spectroscopy and transcranial Doppler ultrasound, respectively. Results were analyzed in the context of available clinical data and a previous study. Results— Frontal CBF, averaged over the patient cohort, decreased by 17% (P=0.034) and 15% (P=0.011) in the ipsilesional and contralesional hemispheres, respectively, when HOB was changed from flat to 30°. Significant (cohort-averaged) changes in blood velocity were not observed. Individually, varying responses to HOB manipulation were observed, including paradoxical increases in CBF with increasing HOB angle. Clinical features, stroke volume, and distance to the optical probe could not explain this paradoxical response. Conclusions— A lower HOB angle results in an increase in cortical CBF without a significant change in arterial flow velocity in AIS, but there is variability across patients in this response. Bedside CBF monitoring with diffuse correlation spectroscopy provides a potential means to individualize interventions designed to optimize CBF in AIS.

Influence of probe pressure on the diffuse correlation spectroscopy blood flow signal: extra-cerebral contributions

A pilot study explores relative contributions of extra-cerebral (scalp/skull) versus brain (cerebral) tissues to the blood flow index determined by diffuse correlation spectroscopy (DCS). Microvascular DCS flow measurements were made on the head during baseline and breath-holding/hyperventilation tasks, both with and without pressure. Baseline (resting) data enabled estimation of extra-cerebral flow signals and their pressure dependencies. A simple two-component model was used to derive baseline and activated cerebral blood flow (CBF) signals, and the DCS flow indices were also cross-correlated with concurrent Transcranial Doppler Ultrasound (TCD) blood velocity measurements. The study suggests new pressure-dependent experimental paradigms for elucidation of blood flow contributions from extra-cerebral and cerebral tissues.

Shape-Based Alignment of Hippocampal Subfields: Evaluation in Postmortem MRI

This paper estimates the accuracy of hippocampal subfield alignment via shape-based normalization. Evaluation takes place in postmortem MRI dataset acquired at 9.4 Tesla with many averages and approximately 0.01 mm3 voxel resolution. Continuous medial representations (cm-reps) are used to establish geometrical correspondences between hippocampal formations in different images; the extent to which these correspondences match up subfields is evaluated and compared to normalization driven by image forces. Shape-based normalization is shown to perform only slightly worse than image-based normalization; this is encouraging because the former is more applicable to in vivo MRI, which typically lacks features that distinguish hippocampal subfields.

Diffuse Correlation Spectroscopy for Flow Assessment & Management of Acute Ischemic Stroke

We used diffuse correlation spectroscopy to assess cerebral autoregulation in acute ischemic stroke patients. Larger perfusion changes were observed in the infarcted hemisphere, and a novel relationship between perfusion and NIHSS was discovered.

A High-Resolution Computational Atlas of the Human Hippocampus from Postmortem Magnetic Resonance Imaging at 9.4 Tesla

This paper describes the construction of a computational anatomical atlas of the human hippocampus. The atlas is derived from high-resolution 9.4 Tesla MRI of postmortem samples. The main subfields of the hippocampus (cornu Ammonis fields CA1, CA2/3; the dentate gyrus; and the vestigial hippocampal sulcus) are labeled in the images manually using a combination of distinguishable image features and geometrical features. A synthetic average image is derived from the MRI of the samples using shape and intensity averaging in the diffeomorphic non-linear registration framework, and a consensus labeling of the template is generated. The agreement of the consensus labeling with manual labeling of each sample is measured, and the effect of aiding registration with landmarks and manually generated mask images is evaluated. The atlas is provided as an online resource with the aim of supporting subfield segmentation in emerging hippocampus imaging and image analysis techniques. An example application examining subfield-level hippocampal atrophy in temporal lobe epilepsy demonstrates the application of the atlas to in vivo studies.

Building an atlas of hippocampal subfields using postmortem MRI

This paper presents preliminary work on the construction of a computational anatomical atlas of the human hippocampus. The atlas is derived from high-resolution 9.4 Tesla MRI of postmortem samples. The main subfields of the hippocampus (cornu Ammonis fields CA1, CA2/3 and CA4; dentate gyrus; and the vestigial hippocampal sulcus) are labeled in the images manually using a combination of distinguishable image features and geometrical features. A synthetic average image is derived from the MRI of the samples using shape and intensity averaging in the diffeomorphic non-linear registration framework, and a consensus labeling of the template is generated. The agreement of the consensus labeling with manual labeling of each sample is measured, and the effect of aiding registration with landmarks and manually generated mask images is evaluated.

Long Term Monitoring of Cerebral Blood Flow in Subarachnoid Hemorrhage Patients Using Diffuse Correlation Spectroscopy

We used diffuse correlation spectroscopy to continuously monitor cerebral blood flow changes in subarachnoid hemorrhage patients due to interventions in the clinic, and present a novel index for assessing cerebral autoregulation in these patients.

SU‐GG‐I‐171: Diffuse Optical Measurements of Blood Oxygenation and Flow for Monitoring CMRO2 in Neonates with Congenital Heart Defects

Purpose: Improve quantification of Cerebral Metabolic Rate of Oxygen (CMR02) by developing a diffuse optical instrument for use in continuous bedside monitoring of neonatal patients with congenital heart defects. Method and Materials: A compact (17″×l7&″×l4&″) Time‐Domain Diffuse Optical Spectroscopy (TD‐DOS) system has been developed and combined with a Diffuse Correlation Spectroscopy (DCS) system. The TD‐DOS system is composed of 3 lasers (685, 785, and 830 nm), 2 PMTs, 2 time correlated single photon counting(TCSPC) cards, and control electronics; the DCS system consists of 2 long‐coherence length 785nm lasers, 8 photon‐counting APDs, and a customized correlator. TD‐DOS allows absolute measurement of optical scattering and absorption, which permits calculation of absolute values for local hemoglobin concentration and tissue oxygen saturation (StO2); DCS measures relative changes in microvascular blood flow. We approximate CMRO2 changes using a compartmentalized model of the cerebral vasculature and Ficks law. However, this calculation relies upon knowledge of baseline physiological properties, namely, blood oxygen saturation and volume, both obtainable from TD‐DOS. Simultaneously, relative changes in cerebral blood flow will be measured by DCS. Together, these diffuse optical modalities will allow us to calculate CMRO2 based on the individual physiological parameters of each subject. Results: Previous works on neonates with congenital heart defects have utilized instrumentation incapable of measuring absolute optical properties. Calculations of CMRO2 were therefore based upon sparse literature reports of baseline quantities obtained from healthy subjects, who are not representative of our patient population. We will demonstrate an improved quantification of CMRO2 by eliminating the questionable assumptions of blood oxygenation and volume in neonatal brains in favor of direct measurements. Conclusion: By combining TD‐DOS measurements of absolute tissueoptical properties with DCS measurements of relative microvascular blood flow, these TD‐DOS data will permit an improved calculation of CMRO2 by providing individualized baseline values.