Manojkumar Saranathan

Hippocampal CA1 apical neuropil atrophy and memory performance in Alzheimer's disease

Memory loss is often the first and most prominent symptom of Alzheimers disease (AD), coinciding with the spread of neurofibrillary pathology from the entorhinal cortex (ERC) to the hippocampus. The apical dendrites of hippocampal CA1 pyramidal neurons, in the stratum radiatum/stratum lacunosum-moleculare (SRLM), are among the earliest targets of this pathology, and atrophy of the CA1-SRLM is apparent in postmortem tissue from patients with mild AD. We previously demonstrated that CA1-SRLM thinning is also apparent in vivo, using ultra-high field 7-Tesla (7T) MRI to obtain high-resolution hippocampal microstructural imaging. Here, we hypothesized that CA1-SRLM thickness would correlate with episodic memory performance among patients with mild AD. We scanned nine patients, using an oblique coronal T2-weighted sequence through the hippocampal body with an in-plane resolution of 220 μm, allowing direct visual identification of subfields - dentate gyrus (DG)/CA3, CA2, CA1, and ERC - and hippocampal strata - SRLM and stratum pyramidale (SP). We present a novel semi-automated method of measuring stratal width that correlated well with manual measurements. We performed multi-domain neuropsychological evaluations that included three tests of episodic memory, yielding composite scores for immediate recall, delayed recall, and delayed recognition memory. Strong correlations occurred between delayed recall performance and the widths of CA1-SRLM (r(2)=0.69; p=0.005), CA1-SP (r(2)=0.5; p=0.034), and ERC (r(2)=0.62; p=0.012). The correlation between CA1-SRLM width and delayed recall lateralized to the left hemisphere. DG/CA3 size did not correlate significantly with any aspect of memory performance. These findings highlight a role for 7T hippocampal microstructural imaging in revealing focal structural pathology that correlates with the central cognitive feature of AD.

DIfferential Subsampling with Cartesian Ordering (DISCO): a high spatio-temporal resolution Dixon imaging sequence for multiphasic contrast enhanced abdominal imaging.

To develop and evaluate a multiphasic contrast‐enhanced MRI method called DIfferential Sub‐sampling with Cartesian Ordering (DISCO) for abdominal imaging.

Coronary angiography by real-time MRI with adaptive averaging

Cardiac and respiratory motion present significant challenges for MR coronary angiography, which have not been completely resolved to date by either breath‐holding or respiratory navigation. Adaptive averaging during real‐time MRI may provide a useful alternative to these techniques. In this method, cross‐correlation is used to automatically identify those real‐time imaging frames in which the vessel is present, and to determine the location of the vessel within each frame. This information is then used for selective averaging of frames to increase the signal‐to‐noise ratio and to improve visualization of the vessel. The correlation theorem was employed to raise the speed of this algorithm by up to two orders of magnitude. Segmenting data collection and reconstruction into subimages allows the extension of this technique to higher spatial resolution. Adaptive averaging provides a robust method for coronary MRI which requires no breath‐holding, navigation, or ECG gating. Magn Reson Med 44:940–946, 2000.

Visualization of intra-thalamic nuclei with optimized white-matter-nulled MPRAGE at 7T.

Novel MR image acquisition strategies have been investigated to elicit contrast within the thalamus, but direct visualization of individual thalamic nuclei remains a challenge because of their small size and the low intrinsic contrast between adjacent nuclei. We present a step-by-step specific optimization of the 3D MPRAGE pulse sequence at 7T to visualize the intra-thalamic nuclei. We first measured T1 values within different sub-regions of the thalamus at 7T in 5 individuals. We used these to perform simulations and sequential experimental measurements (n=17) to tune the parameters of the MPRAGE sequence. The optimal set of parameters was used to collect high-quality data in 6 additional volunteers. Delineation of thalamic nuclei was performed twice by one rater and MR-defined nuclei were compared to the classic Morel histological atlas. T1 values within the thalamus ranged from 1400ms to 1800ms for adjacent nuclei. Using these values for theoretical evaluations combined with in vivo measurements, we showed that a short inversion time (TI) close to the white matter null regime (TI=670ms) enhanced the contrast between the thalamus and the surrounding tissues, and best revealed intra-thalamic contrast. At this particular nulling regime, lengthening the time between successive inversion pulses (TS=6000ms) increased the thalamic signal and contrast and lengthening the α pulse train time (N*TR) further increased the thalamic signal. Finally, a low flip angle during the gradient echo acquisition (α=4°) was observed to mitigate the blur induced by the evolution of the magnetization along the α pulse train. This optimized set of parameters enabled the 3D delineation of 15 substructures in all 6 individuals; these substructures corresponded well with the known anatomical structures of the thalamus based on the classic Morel atlas. The mean Euclidean distance between the centers of mass of MR- and Morel atlas-defined nuclei was 2.67mm (±1.02mm). The reproducibility of the MR-defined nuclei was excellent with intraclass correlation coefficient measured at 0.997 and a mean Euclidean distance between corresponding centers of mass found at first versus second readings of 0.69mm (±0.38mm). This 7T strategy paves the way to better identification of thalamic nuclei for neurosurgical planning and investigation of regional changes in neurological disorders.

Musculoskeletal MRI at 3.0 T and 7.0 T: A comparison of relaxation times and image contrast

OBJECTIVE The purpose of this study was to measure and compare the relaxation times of musculoskeletal tissues at 3.0 T and 7.0 T, and to use these measurements to select appropriate parameters for musculoskeletal protocols at 7.0 T. MATERIALS AND METHODS We measured the T₁ and T₂ relaxation times of cartilage, muscle, synovial fluid, bone marrow and subcutaneous fat at both 3.0 T and 7.0 T in the knees of five healthy volunteers. The T₁ relaxation times were measured using a spin-echo inversion recovery sequence with six inversion times. The T₂ relaxation times were measured using a spin-echo sequence with seven echo times. The accuracy of both the T₁ and T₂ measurement techniques was verified in phantoms at both magnetic field strengths. We used the measured relaxation times to help design 7.0 T musculoskeletal protocols that preserve the favorable contrast characteristics of our 3.0 T protocols, while achieving significantly higher resolution at higher SNR efficiency. RESULTS The T₁ relaxation times in all tissues at 7.0 T were consistently higher than those measured at 3.0 T, while the T₂ relaxation times at 7.0 T were consistently lower than those measured at 3.0 T. The measured relaxation times were used to help develop high resolution 7.0 T protocols that had similar fluid-to-cartilage contrast to that of the standard clinical 3.0 T protocols for the following sequences: proton-density-weighted fast spin-echo (FSE), T₂-weighted FSE, and 3D-FSE-Cube. CONCLUSION The T₁ and T₂ changes were within the expected ranges. Parameters for musculoskeletal protocols at 7.0 T can be optimized based on these values, yielding improved resolution in musculoskeletal imaging with similar contrast to that of standard 3.0 T clinical protocols.

Coronary MR angiography: respiratory motion correction with BACSPIN.

To improve the signal‐to‐noise ratio (SNR) of breath‐held coronary magnetic resonance angiography (CMRA) without increasing the number or duration of breath holds.

Shared Vulnerability of Two Synaptically-Connected Medial Temporal Lobe Areas to Age and Cognitive Decline: A Seven Tesla Magnetic Resonance Imaging Study

The medial temporal lobe (MTL) is the first brain area to succumb to neurofibrillary tau pathology in Alzheimers disease (AD). Postmortem human tissue evaluation suggests that this pathology propagates in an ordered manner, with the entorhinal cortex (ERC) and then CA1 stratum radiatum and stratum lacunosum-moleculare (CA1–SRLM)—two monosynaptically connected structures—exhibiting selective damage. Here, we hypothesized that, if ERC and CA1–SRLM share an early vulnerability to AD pathology, then atrophy should occur in a proportional manner between the two structures. We tested this hypothesis in living humans, using ultra-high field 7.0 T MRI to make fine measurements of MTL microstructure. Among a pool of age-matched healthy controls and patients with amnestic mild cognitive impairment and mild AD, we found a significant correlation between ERC and CA1–SRLM size that could not be explained by global atrophy affecting the MTL. Of the various structures that contribute axons or dendrites into the CA1–SRLM neuropil, only ERC emerged as a significant predictor of CA1–SRLM size in a linear regression analysis. In contrast, other synaptically connected elements of the MTL did not exhibit size correlations. CA1–SRLM and ERC structural covariance was significant for older controls and not patients, whereas the opposite pattern emerged for a correlation between CA1–SRLM and episodic memory performance. Interestingly, CA1–SRLM and ERC were the only MTL structures to atrophy in older controls relative to a younger comparison group. Together, these findings suggest that ERC and CA1–SRLM share vulnerability to both age and AD-associated atrophy.

Improvement of gadoxetate arterial phase capture with a high spatio-temporal resolution multiphase three-dimensional SPGR-dixon sequence

To determine whether a multiphase method with high spatiotemporal resolution (STR) by means of a combination of parallel imaging, pseudorandom sampling and temporal view sharing improves the capture and intensity of gadoxetate arterial phase images as well as lesion enhancement.

Multislice breath-hold spiral magnetic resonance coronary angiography in patients with coronary artery disease: Effect of intravascular contrast medium

First, to apply a breath‐hold multislice 2D spiral magnetic resonance (MR) approach in patients acquiring within 16 heartbeats (acquisition window, 116 msec) a 10‐mm‐thick stack of four slices (resolution, 1.3 × 1.3 mm2); and second, to evaluate the effect of an intravascular Fe‐based contrast medium (CM) on a signal‐to‐noise ratio (SNR) and a contrast‐to‐noise ratio (CNR).

Simultaneous T1 and B1+ Mapping Using Reference Region Variable Flip Angle Imaging

To present a new method that can simultaneously and efficiently measure T1 and B1+ maps using reference region variable flip angle (RR‐VFA) imaging.