Evolution of beta-amyloid induced neuropathology: magnetic resonance imaging and anatomical comparisons in the rodent hippocampus

Alzheimer’s disease (AD) is characterized by the anatomical appearance of β-amyloid (βA) plaques and neurofibrillary tangles. These changes are also associated with cyclical inflammation, oxidative damage and, as inferred from the autopsied brains of patients, progressive injury to neurons. Here, we report the short-term effects of an intrahippocampal injection of the toxic βA peptide fragment 25–35 in rats using quantitative magnetic resonance imaging (MRI) methods. Physiological changes within the cornu ammonis 1 (CA1) region of the hippocampus were monitored using a 1.5 T scanner at time points of 0.25, 1 and 24 h, and 7 and 14 days post injection. Spin echo T2-weighted (T2W) and diffusion weighted (DW) images were sequentially acquired. Apparent diffusion coefficients (ADC) were calculated and compared with histological alterations. A significant elevation in mean ADC values (17%) was observed in the ipsilateral CA1 at 14 days. The ADC changes were associated with disrupted pyramidal cells and nuclear lysis observed in histological sections. The contralateral CA1 exhibited a significant decrease in mean ADC of 15% at 14 days post treatment. Histological changes in the contralateral hippocampus suggested decreased neuronal density. T2W maps revealed no significant differences between the active βA 25–35 fragment and its non-active analog, βA 35–25. In conclusion, these results, based on changes in hippocampal ADC, demonstrate that the βA 25–35 treatment induced pathology consistent with edema and cellular necrosis. This is the first report describing the evolution of AD-like pathology in an animal model using DW imaging.     

Transient global brain ischemia in young and aged rats: differences in severity and progression, but not localisation, of lesions evaluated by magnetic resonance imaging

A model of transient global brain ischemia consisting of bilateral occlusion of common carotid arteries for 10 min and mild hypoxia (15% O₂−85% N₂) for 20 min was studied by means of MRI in young and aged Fischer 344 rats (3–4 and 24–26 months, respectively). Ischemia was assessed by full suppression of spontaneous EEG activity, which reappeared and normalized similarly in the two age-groups. The survival of young with respect to aged rats was considerably higher both at 24 h (20/20, i.e. 100% vs 12/16, i.e. 75%) and at 48 h (16/20, i.e. 80% vs 6/16, i.e. 38%). The localisation of brain lesions, their severity and progression were evaluated by a diffusion-weighted MRI (DWI) sequence at 24 and 48 h post-ischemia. There were no DWI-detectable lesions in eight out of 20 young and two out of 12 aged rats. The localisation of DWI-detected lesions was rather similar in rats of the two age-groups. In fact, the cerebral cortex, mainly parietal, occipital and temporal lobes were damaged in 83% of young and 90% of aged rats. The respective percentages for the thalamus were 83 and 60%, for the striatum 58 and 50%, and for the hippocampus 25 and 30%. The lesions present in the cerebral cortex and the thalamus were considerably more severe in aged than in young rats. In conclusion, in spite of similar localisation of ischemic lesions in the two age-groups, their incidence was higher, appearance more rapid and severity more pronounced in aged with respect to young rats. This resulted in a considerably higher mortality of the former. The overall data indicate that the age issue is very important in experimental ischemia research.     

Diffusion imaging for evaluation of tumor therapies in preclinical animal models

The increasing development of novel targeted therapies for treating solid tumors has necessitated the development of technology to determine their efficacy in preclinical animal models. One such technology that can non-invasively quantify early changes in tumor cellularity as a result of an efficacious therapy is diffusion MRI. In this overview we present some theories as to the origin of diffusion changes as a result of tumor therapy, a robust methodology for acquisition of apparent diffusion coefficient maps and some applications of determining therapeutic efficacy in a variety therapeutic regimens and animal models.     

High-resolution venography of the brain using magnetic resonance imaging

The purpose of this study was to evaluate a non-flow related magnetic resonance imaging method to visualize small veins independent of arteries in the human brain. A long TE, high-resolution 3D gradient echo MR acquisition was used to highlight venous information. The method is based on the paramagnetic property of deoxyhemoglobin and the resulting phase difference between veins and brain parenchyma at long echo times. The MR magnitude images were masked with a phase mask filter to enhance small structure visibility.. Venous information down to sub-pixel vessel diameters of several hundred microns is visible. Venous data are displayed in an angiographic manner using a minimum intensity projection algorithm. Both superficial veins and deep white matter veins are visible. The method has been successfully applied in volunteers. Preliminary results in patients with cerebral arteriovenous malformations indicate its potential in clinical applications. The proposed method is easy to implement and does not require administration of a contrast agent or application of specially designed rf pulses to highlight the veins. Rather it exploits the intrinsic magnetic properties (BOLD-effect) and the prolonged T ^_2* of venous blood. The method may be of diagnostic potential in the assessment of arteriovenous malformations or other vascular venous lesions. © 1998 Elsevier Science B.V. All rights reserved.     

Transient global brain ischemia in the rat: spatial distribution, extension, and evolution of lesions evaluated by magnetic resonance imaging

A newly-developed model of transient global ischemia in the rat was evaluated by magnetic resonance imaging (MRI) in terms of localization of brain lesions, their extent and severity, and temporal evolution. Such a model, consisting of bilateral occlusion of common carotid arteries for 10 minutes and mild hypoxia (15% O₂) for 20 minutes induces delayed neuronal degeneration, necrosis, and gliosis (detected histologically and immunohistochemically). Ischemia was assessed by full suppression of spontaneous electroencephalographic activity. A “hybrid” T₂-/diffusion-weighted MR sequence enhancing more effectively the contrast between injured and intact tissues as compared to T₂-weighted MRI was used at 24, 48, 72, and 96 hours and at 7 days postischemia. Twenty hypoxic-ischemic rats showed a considerable variability in brain damage. In 8, there were no MRI-detectable lesions at any interval. In the other 12 rats, the severity and extension of neuronal damage varied markedly, but the lesions were always localized (monolaterally in 8 and bilaterally in 4 rats) in the occipital, temporal, or parietal cerebral cortex. Mainly, they were of intermediate severity or were severe (as assessed by MRI hyperintensity) and were accompanied by usually less severe lesions in the thalamus and/or caudate putamen. The hippocampus was affected moderately or severely in 4 of 12 rats. In most cases, there was at 48 hours a considerable growth in severity and/or extension of lesions, which usually remained stable at later intervals. In conclusion, MRI allowed us to follow brain lesions during the first week in this relatively simple and noninvasive model of transient global ischemia.     

Integrated RF probe for in vivo multinuclear spectroscopy and functional imaging of rat brain using an 11.7 Tesla 89 mm bore vertical microimager

To acquire high quality in vivo NMR data from rat brain using a vertical 89-mm bore magnet, specially designed NMR probes with integrated RF coils and animal handling capability are required. An RF probe design that is also capable of rat head fixation, body support and suitable for physiology monitoring and maintenance was constructed for an 89 mm bore, 11.7 T, vertical microimager which is equipped with a 57-mm i.d. gradient insert. Design concept and practical aspects of probe construction are described in detail. The device allows accurate and highly reproducible positioning of rat head inside the magnet while providing excellent RF performance. Typical results from fMRI, localized in vivo proton and multinuclear spectroscopy using this probe system are presented.     

Role of magnetic resonance methods in the evaluation of prostate cancer: an Indian perspective

The challenges in detection, localization, and staging of prostate cancer have prompted the investigation of the role of various magnetic resonance (MR) methodologies in a large cohort of men prior to biopsy. The identification of suspicious areas of malignancy was carried out using magnetic resonance imaging (MRI), magnetic resonance spectroscopic imaging (MRSI) and diffusion-weighted imaging (DWI). Our data shows that apparent diffusion coefficient (ADC) may be a reliable marker to differentiate normal, benign, and malignant prostate tissues similar to the metabolite ratio. Also, the combined use of MRSI and DWI improves the diagnosis of prostate cancer. In this review, we present our experience on the use of MRI, MRSI and DWI methods in the assessment of prostate cancer in Indian men. Further, analysis of the comparison of the ADC and the metabolite ratio values reported in the literature across various patient populations are presented. An erratum to this article can be found at     

Effects of riluzole on the evolution of focal cerebral ischemia: a magnetic resonance imaging study

The aim of this study was to investigate the effects of riluzole on the lesion induced by a permanent middle cerebral artery occlusion (MCAO) in rats. Riluzole at 4 or 8 mg/kg i.v. significantly reduced the cortical ischemic brain damage. With the most effective dose of 8 mg/kg, the time evolution of the lesion was assessed by T₂-weighted magnetic resonance imaging (MRI) repeated on the same animals after MCAO. MRI obtained at 24, 48, and 72 hours after MCAO showed a progressive increase of the ischemic lesion, except in the cortex of the riluzole-treated rats (8 mg/kg i.v.). Furthermore, there was no difference between lesion volumes as measured by MRI or by histology. This study indicates that MRI may be a valuable method to quantifyin vivo the neuroprotective profile of a drug.     

Water household of the common carp,Cyprinus carpio, when submitted to an osmotic challenge, as determined by diffusion-weighted magnetic resonance imaging at 7 T

In vivo diffusion-weighted magnetic resonance imaging (MRI) was used to determine the effects of an osmotic challenge (1% NaCl) to a freshwater fish, the common carp (Cyprinus carpio). The imaged region covered organs such as the swimbladder, the liver, the kidney, the intestine, the spinal cord, and muscle tissue. A striking difference between salt-treated and control fish was found in the liver. The apparent diffusion coefficient value of livers from control fish was (0.39±0.16) 10⁻⁹ m²/s and of salt-treated fish was (1.23±0.14) 10⁻⁹ m²/s, which points to an increase in extracellular water content. These results were partially confirmed by a decrease in dry/wet weight ratio of the liver tissue. We also found increased levels of stress proteins in liver tissue. TheQ factor of the applied radiofrequency coil dropped dramatically when we performed experiments with salt-exposed fish, indicating an increased conductivity resulting from the increased ion concentration and osmolarity of the fish. The data on plasma osmolarity of salt-exposed fish confirm a significant osmolarity increase upon salt exposure (from 334 to 430 mOsm/kg) and exceeded the osmolarity of the salt water (324 mOsm/kg), indicating that carp tend to cope with an increased salinity by increasing the internal osmolarity (hyperosmotic regulation). These data demonstrate that diffusion-weighted MRI might be a useful and noninvasive tool in the study of osmotic challenges of aquatic organisms.     

Turbo spin-echo sequences in magnetic resonance imaging of the brain: Physics and applications

Fast SE imaging provides considerable measure time reduction, high signal-to-noise ratios as well as similar contrast behavior compared to conventional SE sequences. Besides TR and TE_eff, echo train length (ETL), interecho time , and-space trajectory determine image contrast and image quality in fast SE sequences. True proton density contrast (CSF hypointense) and not too strong T2 contrast are essential requirements in routine brain MRI. A Turbo SE sequence with very short echo train length (ETL=3), short TE_eff and short interecho time (17 ms), and TR=2000 ms was selected for proton density contrast; a Turbo SE sequence with ETL=7, TE_eff=90 ms, =22 ms, and TR=3250 ms was selected for T₂-weighted images. Using both single-echo Turbo SE sequences yielded 50% measure time reduction compared to the conventional SE technique. Conventional SE and optimized Turbo SE sequences were compared in 150 patients resulting in very similar signal and contrast behavior. Furthermore, reduced flow artifacts in proton density—and especially in T₂-weighted Turbo SE images—and better contrast of high-intensity lesions in proton density-weighted Turbo SE images were found. Slightly reduced edge sharpness—mainly in T₂-weighted Turbo SE images—did not reduce diagnostic reliability. Differences between conventional and Turbo SE images concerning image contrast and quality are explained regarding special features of fast SE technique.Address for correspondence: Institut für Röntgendiagnostik, Klinikum der Universität Regensburg, Franz-Josef-Strauß-Allee 11, 93042 Regensburg, Germany. Additional reprints of this chapter may be obtained from the Reprints Department, Chapman & Hall, One Venn Plaza, New York, NY 10119.     

Focal ischemia in cat brain as studied by diffusion-weighted and dynamic susceptibility-contrast magnetic resonance imaging

Diffusion-weighted and susceptibility-contrast-enhanced magnetic resonance imaging were used to monitor the development of focal ischemia in cat brain. Diffusion-sensitized imaging was used to assess early ischemic tissue damage which was confirmed for the latest time point (12 h) with postmortem histological analysis.T*₂-sensitized FLASH was used to measure the first passage of a bolus of FeO particles. Gamma function fitting of R*₂-time curves resulted in 2D maps of relative hemodynamic parameters, including cerebral blood volume and flow. The present data provide indications for cerebral blood flow thresholds for acute as well as for delayed ischemic tissue damage.     

1H magnetic resonance spectroscopy of the brains of normal infants and after perinatal hypoxia-ischemia

The aims of this study were to define proton (¹H) metabolite peak-area ratios in the brains of normal infants and to investigate abnormalities after perinatal hypoxia-ischemia. Point-resolved spectroscopy (PRESS) data were collected at 2.4 T with an echo time (TE) of 270 ms from 8-ml voxels located in the thalamus or occipito-parietal region. Fourteen normal and 9 asphyxiated infants were studied. The gestational plus postnatal ages (GPA) of these two groups were 31–41 (median 36) and 27–41 (37) weeks, respectively, and the asphyxiated infants were studied aged 0–10 (2) days. Peak-area ratios were determined in the normal infants for choline-containing compounds (Cho), creatine plus phosphocreatine (Cr),N-acetylaspartate (NAA) and lactate (Lac). Lactate was detected in all the normal infants and Lac/NAA was higher in the occipito-parietal region than in the thalamus (p<0.005). Lac/NAA decreased with increasing GPA in both the thalamus (p=0.014) and the occipito-parietal region (p=0.033). In six of the nine asphyxiated infants, Lac/NAA was above 95% confidence intervals for either the thalamus and/or the occipito-parietal region. Of these six infants, two died and three were neurologically abnormal aged 2 months, indicating that elevated Lac/NAA after perinatal hypoxia-ischemia may convey a poor prognosis. Propan-l,2-diol (the phenobarbitone injection medium) was detected at 1.1 ppm in three infants.     

High-resolution magnetic resonance imaging of iron-labeled myoblasts using a standard 1.5-T clinical scanner

Myoblast transplantation is a promising means of restoring cardiac function in infarcted areas. For optimization of transplant protocols, tracking the location and fate of the injected cells is necessary. An attractive imaging modality for this is magnetic resonance imaging (MRI) as it is noninvasive and as iron-labeled myoblasts provide a signal attenuation in T2*-weighted protocols. The aim of this study was to develop an efficient iron-labeling protocol for myoblasts and to visualize single-labeled cells using a clinical 1.5-T scanner. Pig myoblasts were labeled with a superparamagnetic iron oxide (SPIO) agent using a liposome transfection agent. Labeling efficiency, toxicity, cell viability, and proliferative capacity were measured for 10 days. Magnetic resonance (MR) of myoblast cultures used a T2*-weighted three-dimensional protocol with a maximum in-plane resolution of 19.5 × 26.0 m² and 50 m slices. Use of liposomes improved SPIO labeling efficiency. Labeling did not induce toxicity or affect cell viability or proliferation. The cell distribution as observed with light and fluorescence microscopy matched the signal voids observed in the MRI datasets. Liposomes promote fast, nontoxic and efficient SPIO labeling of myoblasts that can be tracked by MRI microscopy in clinical scanners using susceptibility-weighted protocols.     

A review of heart chamber segmentation for structural and functional analysis using cardiac magnetic resonance imaging

Cardiovascular magnetic resonance (CMR) has become a key imaging modality in clinical cardiology practice due to its unique capabilities for non-invasive imaging of the cardiac chambers and great vessels. A wide range of CMR sequences have been developed to assess various aspects of cardiac structure and function, and significant advances have also been made in terms of imaging quality and acquisition times. A lot of research has been dedicated to the development of global and regional quantitative CMR indices that help the distinction between health and pathology. The goal of this review paper is to discuss the structural and functional CMR indices that have been proposed thus far for clinical assessment of the cardiac chambers. We include indices definitions, the requirements for the calculations, exemplar applications in cardiovascular diseases, and the corresponding normal ranges. Furthermore, we review the most recent state-of-the art techniques for the automatic segmentation of the cardiac boundaries, which are necessary for the calculation of the CMR indices. Finally, we provide a detailed discussion of the existing literature and of the future challenges that need to be addressed to enable a more robust and comprehensive assessment of the cardiac chambers in clinical practice.     

High-resolutation magnetic resonance imaging of the endolymphatic duct and sac

An anatomical study was carried out to determine the extent to which magnetic resonance imaging (MRI) could delineate inner ear structures. Anatomical preparations of human petrous temporal bone were examined and compared with the results of MRI in 20 healthy subjects to see whether the structures of the inner ear could be visualized. Imaging of the subjects was carried out in a 1.0-T MRI scanner (Siemens Magnetom Impact). Two stronglyT ₂*-weighted sequences were used: a 3D-PSIF sequence and a 3D-CISS sequence. The 3D data sets were postprocessed using a Maximum Intensity Projection (MIP) program. Our investigations show that it is possible to obtain accurate visualization of structures with a diameter of under 1 mm. In all 20 subjects it was possible to identify both the endolymphatic duct and the endolymphatic sac.     

MR venography of the human brain using susceptibility weighted imaging at very high field strength

Objective We investigate the implications of high magnetic field strength on MR venography based on susceptibility-weighted imaging (SWI) and estimate the optimum echo time to obtain maximum contrast between blood and brain tissue. Materials and methods We measured tissue contrast and relaxation times at 7 T of gray matter, white matter, and venous blood in vivo. Results relaxation times of gray matter, white matter, and venous blood in vivo yielded 32.9 ± 2.3, 27.7 ± 4.3, and 7.4 ± 1.4 ms, respectively. Optimum TE was found to be 15 ms which is supported by theoretical considerations. Using this optimum TE, we acquired 3D high resolution datasets with a large volume coverage in a short measurement time that show very detailed microanatomical structures of the human brain such as intracortical veins and laminar cortical substructures. Conclusions By applying optimised vessel filters (vesselness filter and vessel enhancing diffusion) whole brain MR venograms can be obtained at 7 T with a significantly reduced measurement time compared to 3 T.     

Measurements of left ventricular dimensions using real-time acquisition in cardiac magnetic resonance imaging: comparison with conventional gradient echo imaging

This study investigates the use of real-time acquisition in cardiac magnetic resonance imaging (MRI) for measurements of left ventricular dimensions in comparison with conventional gradient echo acquisition. Thirty-one subjects with a variety of left ventricular morphologies to represent a typical clinical population were studied. Short-axis data sets of the left ventricle (LV) were acquired using a conventional turbo-gradient echo and an ultrafast hybrid gradient echo/echo planar sequence with acquisition in real-time. End-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF) and left ventricular mass (LV mass) were measured. The agreement between the two acquisitions and interobserver, intraobserver and interstudy variabilities were determined. The bias between the two methods was 5.86 ml for EDV, 0.23 ml for ESV and 0.94% for EF. LV mass measurements were significantly lower with the real-time method (mean bias 14.38 g). This is likely to be the result of lower spatial resolution and chemical shift artefacts with the real-time method. Interobserver, intraobserver and interstudy variabilities were low for all parameters. In conclusion, real time acquisition in MRI can provide accurate and reproducible measurements of LV dimensions in subjects with normal as well as abnormal LV morphologies, but LV mass measurements were lower than with conventional gradient echo imaging. Presented in abstract form at the International Society of Magnetic Resonance in Medicine meeting in Denver, Colorado in April 2000.     

Accuracy of computed tomography and magnetic resonance imaging in staging bronchogenic carcinoma

Sixty-three patients with non-small cell bronchogenic carcinoma were prospectively and independently assessed by computed tomography (CT) and magnetic resonance imaging (MRI) before surgery. Images were interpreted by four radiologists who had no knowledge of other imaging studies, except chest x-ray, and were blinded to surgical findings. The data were compared with pathologic and histologic findings. The accuracies of CT and MRI in determining tumor classification and assessing mediastinal and hilar lymph node metastases were compared. Sensitivity of CT in determining T factor was 78%, and specificity was 96%. The values for MRI were 84% and 96%, respectively. There was no significant difference between CT and MRI in staging tumors. MRI is more accurate than CT in diagnosing mediastinal invasion in staging superior sulcus tumors and complex tumors. There was no significant difference between the accuracies of CT and MRI in detecting mediastinal node metastases; the sensitivities were 82% and 90%, respectively, and specificities were 88% and 93%, respectively.     

Identification of metabolic correlates of mild cognitive impairment in Parkinson's disease using magnetic resonance spectroscopic imaging and machine learning

Magnetic Resonance Materials in Physics, Biology and Medicine - To investigate metabolic changes of mild cognitive impairment in Parkinson’s disease (PD-MCI) using proton magnetic resonance...