Milan Hájek

MRI of transplanted pancreatic islets

A promising treatment method for type 1 diabetes mellitus is transplantation of pancreatic islets containing β‐cells. The aim of this study was to develop an MR technique to monitor the distribution and fate of transplanted pancreatic islets in an animal model. Twenty‐five hundred purified and magnetically labeled islets were transplanted through the portal vein into the liver of experimental rats. The animals were scanned using a MR 4.7‐T scanner. The labeled pancreatic islets were clearly visualized in the liver in both diabetic and healthy rats as hypointense areas on T2*‐weighted MR images during the entire measurement period. Transmission electron microscopy confirmed the presence of iron‐oxide nanoparticles inside the cells of the pancreatic islets. A significant decrease in blood glucose levels in diabetic rats was observed; normal glycemia was reached 1 week after transplantation. This study, therefore, represents a promising step toward possible clinical application in human medicine. Magn Reson Med 52:1228–1233, 2004.

Texture analysis of human liver.

To classify healthy and diseased livers by texture analysis (TA).

Water ADC, extracellular space volume, and tortuosity in the rat cortex after traumatic injury.

The diffusion parameters in rat cortex were studied 3–35 days following a cortical stab wound, using diffusion‐weighted MR to determine the apparent diffusion coefficient of water (ADCW) in the tissue, and the real‐time iontophoretic tetramethylammonium (TMA) method to measure the extracellular space (ECS) diffusion parameters: ECS volume fraction α and the ADC of TMA+ (ADCTMA). Severe astrogliosis was found close to the wound, and mild astrogliosis was found in the ipsilateral but not the contralateral cortex. Chondroitin sulfate proteoglycan (CSPG) expression was increased throughout the ipsilateral cortex. In the hemisphere contralateral to the wound, α, ADCTMA, and ADCW were not significantly different from control values. ECS volume fraction was increased only in the vicinity of the wound, in the region of cell death and severe astrogliosis, at 3 and 7 days after injury. However, both ADCTMA and ADCW were significantly decreased after lesion in the vicinity of the wound as well as in the rest of the ipsilateral hemisphere distant from the wound. Thus, both ADCW and ADCTMA decreased in regions wherein α did not change but CSPG increased. An increase in extracellular matrix expression may therefore impose diffusion barriers for water as well as for TMA molecules. Magn Reson Med 48:994–1003, 2002.

Magnetic resonance tracking of human CD34+ progenitor cells separated by means of immunomagnetic selection and transplanted into injured rat brain.

Magnetic resonance imaging (MRI) provides a noninvasive method for studying the fate of transplanted cells in vivo. We studied whether superparamagnetic nanoparticles (CD34 microbeads), used clinically for specific magnetic sorting, can be used as a magnetic cell label for in vivo cell visualization. Human cells from peripheral blood were selected by CliniMACS® CD34 Selection Technology (Miltenyi). Purified CD34+ cells were implanted into rats with a cortical photochemical lesion, contralaterally to the lesion. Twenty-four hours after grafting, the implanted cells were detected in the contralateral hemisphere as a hypointense spot on T2 weighted images; the hypointensity of the implant decreased during the first week. At the lesion site we observed a hypointensive signal 10 days after grafting that persisted for the next 3 weeks, until the end of the experiment. Prussian blue and anti-human nuclei staining confirmed the presence of magnetically labeled human cells in the corpus callosum and in the lesion 4 weeks after grafting. CD34+ cells were also found in the subventricular zone (SVZ). Human DNA (a human-specific 850 base pair fragment of α-satellite DNA from human chromosome 17) was detected in brain tissue sections from the lesion using PCR, confirming the presence of human cells. Our results show that CD34 microbeads superparamagnetic nanoparticles can be used as a magnetic cell label for in vivo cell visualization. The fact that microbeads coated with different commercially available antibodies can bind to specific cell types opens extensive possibilities for cell tracking in vivo.

Classification of calf muscle MR images by texture analysis.

Aim: To evaluate a method of texture analysis (TA) for the description of magnetic resonance (MR) images of healthy and diseased calf muscles and to compare this method with standard radiological evaluation. Methods: A total of 93 subjects (20 controls, seven healthy children of hypertonic parents, five diabetic patients and 61 subjects with muscle malfunction of various origin) underwent MR imaging of the calf muscle and texture analysis of images was performed. The results of TA were analysed by t-statistics and principal component analysis. Images of subjects were divided into four groups according to the assessment of three radiologists and this categorization of subjects was compared with the results from TA. Results: We extracted seven features (from a total number of 282) which were successfully used for the description of the texture of T1w MR images of calf muscles. The results of classification by TA are in 80% agreement with the categorization made by the radiologists. In some cases, TA is able to describe changes not apparent by visual inspection. Conclusion: The TA of MR images of calf muscles can be used for the objective description of changes in muscles and could help radiologists to distinguish between healthy and diseased tissue.

Metabolic Changes in the Thalamus after Spinal Cord Injury Followed by Proton MR Spectroscopy

Our study followed the changes in thalamic nuclei metabolism, hindlimb sensitivity to thermal stimulation, and locomotor function after spinal cord injury (SCI). MR spectroscopy (MRS) was used to examine the thalamic nuclei of rats 1 day before and 1, 3, 6, and 15 days after SCI or sham surgery. All animals were tested before MRS measurements for motor performance and thermal sensitivity. SCI induced by balloon compression caused complete paraplegia from the first to third day, followed by partial functional recovery during the second week. MRS revealed an increase in N‐acetylaspartate (NAA) concentration in the thalamic nuclei on the first day after SCI, which decreased by the third day. The data also showed an increase in inositol (Ins), glutamate, and creatine (Cr) concentrations on the third day postinjury; the Ins concentration remained elevated on the sixth day. In sham‐operated animals an increase in NAA concentration was observed on the sixth and fifteenth days after surgery and an increase in Cr concentration on the third day. A positive correlation between Ins concentration and hindlimb sensitivity in both SCI and sham‐operated animals suggests changes in glial activity, while changes in NAA levels may indicate the response of thalamic neuronal cells to injury. Magn Reson Med, 2008.

Association between cardiac energy metabolism and gain of left ventricular mass in Fabry disease

Left ventricular (LV) hypertrophy is the hallmark of cardiac involvement in Fabry disease (FD). However, its pathogenesis is not clearly understood as pathologic substrate accumulation represents only 1-2% of the total cardiac mass. Abnormal myocardial energy metabolism has been previously demonstrated in different forms of cardiomyopathies. We hypothesized that myocardial energy status at the time of diagnosis could have a relationship to gain of LV mass in FD. In the group of 16 affected subjects, the indicators of energetic state of cardiac muscle determined by magnetic resonance spectroscopy showed significant negative correlation with annual increase in LV mass, evaluated during long-term follow-up (8 ± 3 years). Myocardial energy metabolism may therefore represent one of the mechanisms contributing to development of FD-related cardiomyopathy.

Linear microstrip surface coil for MR imaging of the rat spinal cord at 4.7 T

A new design of RF coil based on a quasi-transverse electromagnetic field is described. The coil was developed for the acquisition of MR images of the rat spinal cord at 4.7 T. Different materials for the construction of the coil were tested, and the best results were obtained with Teflon. The design of the microstrip coil enables the investigator to change the length of the coil in a longitudinal direction and yields a relatively high signal-to-noise ratio due to the restricted field of view. Low RF field penetration depth also helps in suppressing motion artifacts generated by, e.g., breathing or heartbeats.

Improved detection of pancreatic islets in vivo using double contrast

The transplantation of pancreatic islets containing β-cells, which produce insulin, is an alternative approach to the treatment of type 1 diabetes mellitus. The non-invasive visualization of transplanted islets can be performed using MRI; however, this requires labeling of the islets with a suitable contrast agent prior to transplantation. The detection of islets labeled by iron oxide-based contrast agents and transplanted into the liver tissue can be significantly improved using the intravenous administration of a suitable gadolinium contrast agent prior to MRI. The applied contrast agent not only improves the contrast-to-noise ratio, but also eliminates artifacts that may lead to an overestimation of the number of hypointense spots and their area; thus it improves the accuracy of automated and semi-automated procedures used for transplanted islet segmentation and quantification.

Comparison of MR spectroscopy and MR imaging with contrast agent in children with cerebral astrocytomas

Abstract We studied 33 patients with astrocytomas of different grades (68 examinations) by magnetic resonance imaging (MRI) and proton MR spectroscopy (1H-MRS). We found that in 80% of the spectra, the presence of signals in the area of 0.8–1.5 ppm, assigned to lipids/lactate in 1H-MR spectra, correlated with signal enhancement after Gd-DTPA administration. We suggest that visibility of lipid/lactate signals could be due to blood–brain barrier damage, which is characterized by contrast agent enhancement.