Quantitative magnetic resonance imaging of capillary water permeability and regional blood volume with an intravascular MR contrast agent.

A novel method is presented to simultaneously measure the permeability surface area product of water (PS), also known as capillary diffusion capacity, and the regional blood volume (RBV). It is based on magnetic resonance imaging of the longitudinal relaxation times of tissue and blood at different concentrations of an intravascular MR contrast agent. PS and RBV were measured in vivo in different regions of the brain and the skeletal muscle of the rat. The average PS values (n = 5) obtained in cerebral cortex, corpus callosum, hippocampus, thalamus, jaw muscle, and tongue muscle were 3.31 +/- 0.20, 1.81 +/- 0.25, 3.37 +/- 0.36, 3.68 +/- 0.44, 10.6 +/- 1.1, and 14.1 +/- 2.51 ml x min(-1) x g(-1), respectively. The corresponding average RBV values were 1.63 +/- 0.18, 1.22 +/- 0.25, 3.30 +/- 0.37, 3.03 +/- 0.36, 1.66 +/- 0.30, and 1.38 +/- 0.33 ml x 100 g(-1). These results are in good agreement with previously reported literature values obtained by means of autoradiography.

Partial inhibition of AT-EAE by an antibody to ICAM-1: clinico-histological and MRI studies.

The role of quantitative proton magnetic resonance imaging (MRI) for the evaluation of immunopathological lesions in the CNS was studied in adoptively transferred experimental allergic encephalomyelitis (AT-EAE). We utilized a recently established treatment model, inhibition of the cell adhesion molecule ICAM-1 by the monoclonal antibody 1A-29. The animals were scanned on days 3, 5 and 7 after injection of encephalitogenic T-cells, before and after bolus injection of Gd-DTPA by performing T1-measurements to assess the integrity of the blood-brain barrier (BBB). On day 7, immunohistochemistry was performed looking for T-cells, activated macrophages, and albumin staining. There was clinical evidence of partial inhibition of AT-EAE in rats treated with antibodies against ICAM-1. This finding was in line with a significantly reduced number of T-cells in the medulla. However, the number of activated macrophages and the distribution of albumin did not differ from untreated AT-EAE animals. The histological findings are in agreement with the MRI data before and after Gd-DTPA injection which were similar in treated and untreated AT-EAE rats on day 3 and 5. On day 7 after Gd-DTPA injection there was evidence of a delayed breakdown of the BBB in the treated rats. The observation of a dissociation of clinical and MRI findings, especially evidence of Gd-enhancement despite clinical improvement, may be important in the context of interpreting MRI studies in MS patients in treatment trials.

Magnetic resonance imaging investigation of blood-brain barrier damage in adoptive transfer experimental autoimmune encephalomyelitis.

Recent advances in fast magnetic resonance imaging (MRI) techniques have allowed quantification of parameters such as T1 relaxation time, which can be modified by changes in the water content of a tissue. We have used this new method to study the evolution of blood-brain barrier (BBB) changes after adoptive transfer of MBP-specific (AT-EAE) and ovalbumin-specific T cell lines in Lewis rats. Measurable changes in T1 relaxation time suggesting widespread increase in BBB permeability were found, starting on day 3 post inoculation (p.i.), in the midbrain and brainstem of AT-EAE rats. In addition, we noted a significant decrease in T1 relaxation time before injection of a paramagnetic agent, in the cisternal cerebrospinal fluid (CSF) of diseased animals, starting on day 5 p.i. In vitro measurement of T1 in CSF containing various concentrations of albumin, IgM and glucose showed that, at physiological concentrations, a T1 decrease is mainly associated with an increase in albumin concentration. A moderate increase in BBB and blood-CSF barrier permeability was found as early as 4-8 h p.i., in rats injected with MBP-specific as in animals injected with ovalbumin-specific T cell lines, suggesting a non-specific mechanism. Experimental MRI may become a powerful tool to sequentially analyse changes in barrier dynamics, for example following pharmacological intervention.

Quantification of regional blood volumes by rapid T1 mapping.

A new method is presented for the quantitative determination of regional blood volumes in vivo. It is based on rapid quantitative T1 mapping by Snapshot FLASH MRI combined with the injection of an intravascular MR contrast agent. Regional blood volumes in four different tissues of the rat (skeletal muscle, heart, liver, kidney) were determined in an in vivo experiment.

T1 maps by K-space reduced snapshot-FLASH MRI.

The T1 maps evaluated from k-space reduced Snapshot fast low angle shot (FLASH) images provide high contrast parameter images for tissue characterization in vivo of any body region. An algorithm for computing T1 values that allows a fast and reliable evaluation of T1 maps and yields reproducible values of tissue parameters in MR imaging is presented. The algorithm combined with the Snapshot FLASH inversion recovery imaging sequence permits a precise determination of T1 values, even for T1 times as low as 50 ms. Comparison with a spectroscopical inversion recovery method on identical phantoms demonstrates the accuracy of this technique. With its total acquisition time of approximately 2 s, IR Snapshot FLASH is fast enough to be used in monitoring fast T1 dynamics.

Cell and tissue responses of a murine tumour to phthalocyanine-mediated photodynamic therapy.

Mice bearing a subcutaneously growing tumour (Colo 26) were injected intravenously with the photosensitiser chloroaluminum sulphonated phthalocyanine (5 mg/kg) 24 h prior to irradiating the tumour with laser light (675 nm; 50mW, 100 J/tumour). Energy status of the tumour, as assessed by the loss of high energy phosphates in the 31P-nuclear magnetic resonance spectra, was altered dramatically following treatment, such that the ATP fell to undetectable levels within 1 h of light irradiation. However, assessment of the clonogenic capacity of neoplastic cells isolated from dissociated tumours showed that these rapid changes in cellular metabolism were not reflected in similar rapid changes in cell viability. Reductions in clonogenic capacity, which fell to less than 0.1% of control values at 24h postirradiation, closely mirrored those resulting from the cessation of vascular perfusion. Evaluation of tumour blood flow, using the technique of hydrogen washout, showed that the treatment protocol evoked a gradual and selective reduction in flow within the tumour resulting in complete vascular stasis by approximately 5 h after treatment. The results indicate that while chloroaluminum sulphonated phthalocyanine-mediated photodynamic therapy caused early metabolic damage in neoplastic cells, loss of viability paralleled the induction of complete inhibition of vascular flow in the tumour.

Identification of tumor hemorrhage in an animal model using spin echoes and gradient echoes.

We report here how magnetic resonance imaging can be used to gain definitive information about tissue pathology by the combined use of spin-echo and gradient-echo sequences. We also show how artifacts arising from respiratory motion can be eliminated by using a simple respiratory gating technique.