Marcel Warntjes

Magnetic resonance imaging goes postmortem: noninvasive detection and assessment of myocardial infarction by postmortem MRI

ObjectiveTo investigate the performance of postmortem magnetic resonance imaging (pmMRI) in identification and characterization of lethal myocardial infarction in a non-invasive manner on human corpses.Materials and MethodsBefore forensic autopsy, 20 human forensic corpses were examined on a 1.5-T system for the presence of myocardial infarction. Short axis, transversal and longitudinal long axis images (T1-weighted; T2-weighted; PD-weighted) were acquired in situ. In subsequent autopsy, the section technique was adapted to short axis images. Histological investigations were conducted to confirm autopsy and/or radiological diagnoses.ResultsNineteen myocardial lesions were detected and age staged with pmMRI, of which 13 were histologically confirmed (chronic, subacute and acute). Six lesions interpreted as peracute by pmMRI showed no macroscopic or histological finding. Five of the six peracute lesions correlated well to coronary pathology, and one case displayed a severe hypertrophic alteration.ConclusionpmMRI reliably demonstrates chronic, subacute and acute myocardial infarction in situ. In peracute cases pmMRI may display ischemic lesions undetectable at autopsy and routine histology. pmMRI has the potential to substantiate autopsy and to counteract the loss of reliable information on causes of death due to the recent disappearance of the clinical autopsy.

Evaluation of Automatic Measurement of the Intracranial Volume Based on Quantitative MR Imaging

BACKGROUND AND PURPOSE: Brain size is commonly described in relation to ICV, whereby accurate assessment of this quantity is fundamental. Recently, an optimized MR sequence (QRAPMASTER) was developed for simultaneous quantification of T1, T2, and proton density. ICV can be measured automatically within minutes from QRAPMASTER outputs and a dedicated software, SyMRI. Automatic estimations of ICV were evaluated against the manual segmentation. MATERIALS AND METHODS: In 19 healthy subjects, manual segmentation of ICV was performed by 2 neuroradiologists (Obs1, Obs2) by using QBrain software and conventional T2-weighted images. The automatic segmentation from the QRAPMASTER output was performed by using SyMRI. Manual corrections of the automatic segmentation were performed (corrected-automatic) by Obs1 and Obs2, who were blinded from each other. Finally, the repeatability of the automatic method was evaluated in 6 additional healthy subjects, each having 6 repeated QRAPMASTER scans. The time required to measure ICV was recorded. RESULTS: No significant difference was found between reference and automatic (and corrected-automatic) ICV (P > .25). The mean difference between the reference and automatic measurement was −4.84 ± 19.57 mL (or 0.31 ± 1.35%). Mean differences between the reference and the corrected-automatic measurements were −0.47 ± 17.95 mL (−0.01 ± 1.24%) and −1.26 ± 17.68 mL (−0.06 ± 1.22%) for Obs1 and Obs2, respectively. The repeatability errors of the automatic and the corrected-automatic method were <1%. The automatic method required 1 minute 11 seconds (SD = 12 seconds) of processing. Adding manual corrections required another 1 minute 32 seconds (SD = 38 seconds). CONCLUSIONS: Automatic and corrected-automatic quantification of ICV showed good agreement with the reference method. SyMRI software provided a fast and reproducible measure of ICV.

Gd2O3 nanoparticles in hematopoietic cells for MRI contrast enhancement

As the utility of magnetic resonance imaging (MRI) broadens, the importance of having specific and efficient contrast agents increases and in recent time there has been a huge development in the fields of molecular imaging and intracellular markers. Previous studies have shown that gadolinium oxide (Gd2O3) nanoparticles generate higher relaxivity than currently available Gd chelates: In addition, the Gd2O3 nanoparticles have promising properties for MRI cell tracking. The aim of the present work was to study cell labeling with Gd2O3 nanoparticles in hematopoietic cells and to improve techniques for monitoring hematopoietic stem cell migration by MRI. Particle uptake was studied in two cell lines: the hematopoietic progenitor cell line Ba/F3 and the monocytic cell line THP-1. Cells were incubated with Gd2O3 nanoparticles and it was investigated whether the transfection agent protamine sulfate increased the particle uptake. Treated cells were examined by electron microscopy and MRI, and analyzed for particle content by inductively coupled plasma sector field mass spectrometry. Results showed that particles were intracellular, however, sparsely in Ba/F3. The relaxation times were shortened with increasing particle concentration. Relaxivities, r1 and r2 at 1.5 T and 21°C, for Gd2O3 nanoparticles in different cell samples were 3.6–5.3 s−1 mM−1 and 9.6–17.2 s−1 mM−1, respectively. Protamine sulfate treatment increased the uptake in both Ba/F3 cells and THP-1 cells. However, the increased uptake did not increase the relaxation rate for THP-1 as for Ba/F3, probably due to aggregation and/or saturation effects. Viability of treated cells was not significantly decreased and thus, it was concluded that the use of Gd2O3 nanoparticles is suitable for this type of cell labeling by means of detecting and monitoring hematopoietic cells. In conclusion, Gd2O3 nanoparticles are a promising material to achieve positive intracellular MRI contrast; however, further particle development needs to be performed.

Rapid T1 quantification based on 3D phase sensitive inversion recovery

BackgroundIn Contrast Enhanced Magnetic Resonance Imaging fibrotic myocardium can be distinguished from healthy tissue using the difference in the longitudinal T1 relaxation after administration of Gadolinium, the so-called Late Gd Enhancement. The purpose of this work was to measure the myocardial absolute T1 post-Gd from a single breath-hold 3D Phase Sensitivity Inversion Recovery sequence (PSIR). Equations were derived to take the acquisition and saturation effects on the magnetization into account.MethodsThe accuracy of the method was investigated on phantoms and using simulations. The method was applied to a group of patients with suspected myocardial infarction where the absolute difference in relaxation of healthy and fibrotic myocardium was measured at about 15 minutes post-contrast. The evolution of the absolute R1 relaxation rate (1/T1) over time after contrast injection was followed for one patient and compared to T1 mapping using Look-Locker. Based on the T1 maps synthetic LGE images were reconstructed and compared to the conventional LGE images.ResultsThe fitting algorithm is robust against variation in acquisition flip angle, the inversion delay time and cardiac arrhythmia. The observed relaxation rate of the myocardium is 1.2 s-1, increasing to 6 - 7 s-1 after contrast injection and decreasing to 2 - 2.5 s-1 for healthy myocardium and to 3.5 - 4 s-1 for fibrotic myocardium. Synthesized images based on the T1 maps correspond very well to actual LGE images.ConclusionsThe method provides a robust quantification of post-Gd T1 relaxation for a complete cardiac volume within a single breath-hold.

Simultaneous three-dimensional myocardial T1 and T2 mapping in one breath hold with 3D-QALAS

BackgroundQuantification of the longitudinal- and transverse relaxation time in the myocardium has shown to provide important information in cardiac diagnostics. Methods for cardiac relaxation time mapping generally demand a long breath hold to measure either T1 or T2 in a single 2D slice. In this paper we present and evaluate a novel method for 3D interleaved T1 and T2 mapping of the whole left ventricular myocardium within a single breath hold of 15 heartbeats.MethodsThe 3D-QALAS (3D-quantification using an interleaved Look-Locker acquisition sequence with T2 preparation pulse) is based on a 3D spoiled Turbo Field Echo sequence using inversion recovery with interleaved T2 preparation. Quantification of both T1 and T2 in a volume of 13 slices with a resolution of 2.0x2.0x6.0 mm is obtained from five measurements by using simulations of the longitudinal magnetizations Mz. This acquisition scheme is repeated three times to sample k-space. The method was evaluated both in-vitro (validated against Inversion Recovery and Multi Echo) and in-vivo (validated against MOLLI and Dual Echo).ResultsIn-vitro, a strong relation was found between 3D-QALAS and Inversion Recovery (R = 0.998; N = 10; p < 0.01) and between 3D-QALAS and Multi Echo (R = 0.996; N = 10; p < 0.01). The 3D-QALAS method showed no dependence on e.g. heart rate in the interval of 40–120 bpm. In healthy myocardium, the mean T1 value was 1083 ± 43 ms (mean ± SD) for 3D-QALAS and 1089 ± 54 ms for MOLLI, while the mean T2 value was 50.4 ± 3.6 ms 3D-QALAS and 50.3 ± 3.5 ms for Dual Echo. No significant difference in in-vivo relaxation times was found between 3D-QALAS and MOLLI (N = 10; p = 0.65) respectively 3D-QALAS and Dual Echo (N = 10; p = 0.925) for the ten healthy volunteers.ConclusionsThe 3D-QALAS method has demonstrated good accuracy and intra-scan variability both in-vitro and in-vivo. It allows rapid acquisition and provides quantitative information of both T1 and T2 relaxation times in the same scan with full coverage of the left ventricle, enabling clinical application in a broader spectrum of cardiac disorders.

SyMRI of the Brain: Rapid Quantification of Relaxation Rates and Proton Density, With Synthetic MRI, Automatic Brain Segmentation, and Myelin Measurement

Abstract Conventional magnetic resonance images are usually evaluated using the image signal contrast between tissues and not based on their absolute signal intensities. Quantification of tissue parameters, such as relaxation rates and proton density, would provide an absolute scale; however, these methods have mainly been performed in a research setting. The development of rapid quantification, with scan times in the order of 6 minutes for full head coverage, has provided the prerequisites for clinical use. The aim of this review article was to introduce a specific quantification method and synthesis of contrast-weighted images based on the acquired absolute values, and to present automatic segmentation of brain tissues and measurement of myelin based on the quantitative values, along with application of these techniques to various brain diseases. The entire technique is referred to as “SyMRI” in this review. SyMRI has shown promising results in previous studies when used for multiple sclerosis, brain metastases, Sturge-Weber syndrome, idiopathic normal pressure hydrocephalus, meningitis, and postmortem imaging.

Modeling the Presence of Myelin and Edema in the Brain Based on Multi-Parametric Quantitative MRI

The aim of this study was to present a model that uses multi-parametric quantitative MRI to estimate the presence of myelin and edema in the brain. The model relates simultaneous measurement of R1 and R2 relaxation rates and proton density to four partial volume compartments, consisting of myelin partial volume, cellular partial volume, free water partial volume, and excess parenchymal water partial volume. The model parameters were obtained using spatially normalized brain images of a group of 20 healthy controls. The pathological brain was modeled in terms of the reduction of myelin content and presence of excess parenchymal water, which indicates the degree of edema. The method was tested on spatially normalized brain images of a group of 20 age-matched multiple sclerosis (MS) patients. Clear differences were observed with respect to the healthy controls: the MS group had a 79 mL smaller brain volume (1069 vs. 1148 mL), a 38 mL smaller myelin volume (119 vs. 157 mL), and a 21 mL larger excess parenchymal water volume (78 vs. 57 mL). Template regions of interest of various brain structures indicated that the myelin partial volume in the MS group was 1.6 ± 1.5% lower for gray matter (GM) structures and 2.8 ± 1.0% lower for white matter (WM) structures. The excess parenchymal water partial volume was 9 ± 10% larger for GM and 5 ± 2% larger for WM. Manually placed ROIs indicated that the results using the template ROIs may have suffered from loss of anatomical detail due to the spatial normalization process. Examples of the application of the method on high-resolution images are provided for three individual subjects: a 45-year-old healthy subject, a 72-year-old healthy subject, and a 45-year-old MS patient. The observed results agreed with the expected behavior considering both age and disease. In conclusion, the proposed model may provide clinically important parameters, such as the total brain volume, degree of myelination, and degree of edema, based on a single qMRI acquisition with a clinically acceptable scan time.

Detection and differentiation of early acute and following age stages of myocardial infarction with quantitative post-mortem cardiac 1.5 T MR

Recently, quantitative MR sequences have started being used in post-mortem imaging. The goal of the present study was to evaluate if early acute and following age stages of myocardial infarction can be detected and discerned by quantitative 1.5T post-mortem cardiac magnetic resonance (PMCMR) based on quantitative T1, T2 and PD values. In 80 deceased individuals (25 female, 55 male), a cardiac MR quantification sequence was performed prior to cardiac dissection at autopsy in a prospective study. Focal myocardial signal alterations detected in synthetically generated MR images were MR quantified for their T1, T2 and PD values. The locations of signal alteration measurements in PMCMR were targeted at autopsy heart dissection and cardiac tissue specimens were taken for histologic examinations. Quantified signal alterations in PMCMR were correlated to their according histologic age stage of myocardial infarction. In PMCMR seventy-three focal myocardial signal alterations were detected in 49 of 80 investigated hearts. These signal alterations were diagnosed histologically as early acute (n=39), acute (n=14), subacute (n=10) and chronic (n=10) age stages of myocardial infarction. Statistical analysis revealed that based on their quantitative T1, T2 and PD values, a significant difference between all defined age groups of myocardial infarction can be determined. It can be concluded that quantitative 1.5T PMCMR quantification based on quantitative T1, T2 and PD values is feasible for characterization and differentiation of early acute and following age stages of myocardial infarction.

Post-mortem 1.5T MR quantification of regular anatomical brain structures

Recently, post-mortem MR quantification has been introduced to the field of post-mortem magnetic resonance imaging. By usage of a particular MR quantification sequence, T1 and T2 relaxation times and proton density (PD) of tissues and organs can be quantified simultaneously. The aim of the present basic research study was to assess the quantitative T1, T2, and PD values of regular anatomical brain structures for a 1.5T application and to correlate the assessed values with corpse temperatures. In a prospective study, 30 forensic cases were MR-scanned with a quantification sequence prior to autopsy. Body temperature was assessed during MR scans. In synthetically calculated T1, T2, and PD-weighted images, quantitative T1, T2 (both in ms) and PD (in %) values of anatomical structures of cerebrum (Group 1: frontal gray matter, frontal white matter, thalamus, internal capsule, caudate nucleus, putamen, and globus pallidus) and brainstem/cerebellum (Group 2: cerebral crus, substantia nigra, red nucleus, pons, cerebellar hemisphere, and superior cerebellar peduncle) were assessed. The investigated brain structures of cerebrum and brainstem/cerebellum could be characterized and differentiated based on a combination of their quantitative T1, T2, and PD values. MANOVA testing verified significant differences between the investigated anatomical brain structures among each other in Group 1 and Group 2 based on their quantitative values. Temperature dependence was observed mainly for T1 values, which were slightly increasing with rising temperature in the investigated brain structures in both groups. The results provide a base for future computer-aided diagnosis of brain pathologies and lesions in post-mortem magnetic resonance imaging.

Increased fMRI Sensitivity at Equal Data Burden Using Averaged Shifted Echo Acquisition

There is growing evidence as to the benefits of collecting BOLD fMRI data with increased sampling rates. However, many of the newly developed acquisition techniques developed to collect BOLD data with ultra-short TRs require hardware, software, and non-standard analytic pipelines that may not be accessible to all researchers. We propose to incorporate the method of shifted echo into a standard multi-slice, gradient echo EPI sequence to achieve a higher sampling rate with a TR of <1 s with acceptable spatial resolution. We further propose to incorporate temporal averaging of consecutively acquired EPI volumes to both ameliorate the reduced temporal signal-to-noise inherent in ultra-fast EPI sequences and reduce the data burden. BOLD data were collected from 11 healthy subjects performing a simple, event-related visual-motor task with four different EPI sequences: (1) reference EPI sequence with TR = 1440 ms, (2) shifted echo EPI sequence with TR = 700 ms, (3) shifted echo EPI sequence with every two consecutively acquired EPI volumes averaged and effective TR = 1400 ms, and (4) shifted echo EPI sequence with every four consecutively acquired EPI volumes averaged and effective TR = 2800 ms. Both the temporally averaged sequences exhibited increased temporal signal-to-noise over the shifted echo EPI sequence. The shifted echo sequence with every two EPI volumes averaged also had significantly increased BOLD signal change compared with the other three sequences, while the shifted echo sequence with every four EPI volumes averaged had significantly decreased BOLD signal change compared with the other three sequences. The results indicated that incorporating the method of shifted echo into a standard multi-slice EPI sequence is a viable method for achieving increased sampling rate for collecting event-related BOLD data. Further, consecutively averaging every two consecutively acquired EPI volumes significantly increased the measured BOLD signal change and the subsequently calculated activation map statistics.