In vivo mapping of fractional plasma volume (fpv) and endothelial transfer coefficient (Kps) in solid tumors using a macromolecular contrast agent: correlation with histology and ultrastructure.

Contrast-enhanced MRI, immunostaining and electron microscopy were used to detect areas of intense angiogenesis in experimental tumors. This work was also aimed at evaluating the possible effect of the surrounding tissues on tumor microvasculature and at studying the penetration of macromolecules in avascular areas. Human colon carcinoma cells were implanted in subcutaneous tissue of nude mice. Dynamic T(1)-weigthed 3D pulse sequences were acquired before and after administration of Gd-DTPA-albumin to obtain parametric maps of fractional plasma volume (fpv) and transendothelial permeability (Kps). The maps suggested that tumor can be subdivided into 4 zones located in the peripheral rim (zones I-II) or in the core (zones III-IV) of the tumor itself. Significant differences (p<0.001) were found in the values of Kps and fpv of zones I-II with respect to zones III-IV. In the peripheral rim, permeability was significantly higher (p<0.01) in the muscle-peripheral region (zone I) with respect to the skin-peripheral region (zone II). In areas with high Kps, histological and ultrastructural examination revealed clusters of newly formed vessels and signs of intense permeability. Numerous vascular vesicular organs were visible in these areas. In the tumoral core, analysis of the microcirculatory parameters revealed regions with mild permeability (zone III) and regions with negligible permeability (zone IV). These 2 zones were discriminated by the average value of Kps (p<0.05), while their fpv was not significantly different. Upon histological examination, the tumoral core exhibited necrotic areas; CD31 immunocytochemistry exhibited that it was diffusely hypovascularized with large avascular areas. Upon ultrastructural examination, capillaries were rarely visible and exhibited signs of endothelial cell damage. The results suggest that segmentation based on microvascular parameters detects in vivo zones characterized by immunocytochemical and ultrastructural aspects of intense angiogenesis. The finding that a certain amount of contrast agent penetrates in the tumoral core suggests that high oncotic and hydrostatic pressure only partially hinders the penetration of macromolecules.

Dynamic MRI reveals that the magnitude of the ischemia-related enhancement in skeletal muscle is age-dependent.

This study was designed to evaluate the influence of age on the dynamic contrast-enhanced MRI of ischemic tissue. A well-established model of peripheral arterial insufficiency (i.e., the rat hindlimb ischemia after removal of femoral artery) in different age groups (i.e., young, presenescent, and senescent rats) was studied. The analysis of the MR signal demonstrated a marked accumulation of a contrast agent (Gd-DTPA) in the ischemic leg (ischemia-related enhancement, IRE). IRE was an age-related event: 4-month-old rats showed a strong IRE while 12-month-old rats and 20-month old rats showed a significantly reduced IRE in comparison to young animals. Histological analysis of the ischemic muscles revealed that there was no evidence of significant necrosis of the muscle tissue but only a weak interstitial fibrosis; CD31-immunostaining revealed a preserved microcirculatory bed.

Magnetic resonance imaging of the rat Harderian gland.

The intra-orbital lacrimal gland (Harderian gland, or HG) of the female rat was studied by magnetic resonance imaging (MRI) to evaluate whether MRI can be used to visualize the gland in vivo and localized-1H-spectroscopy detect its lipid content. The results were correlated with post-mortem anatomical sections, and with light and electron microscopy. On MRI, HG presented as a mass located between the ocular bulb and the orbit. In strongly T2W sequences the secretory structures had a reduced signal while intraparenchymal connective tissue was visible. T2-quantitative maps values of HG (60.12 +/- 8.15 ms, mean +/- SD) were different from other tissues (i.e. muscular tissue, T2 = 44.79 +/- 3.43 ms and olfactory bulb, T2 = 79.26 +/- 4.25 ms). In contrast-enhanced-MRI, HG had a signal-intensity-drop of 0.074 +/- 0.072 (mean +/- SD), after injection of AMI-25, significantly different from the muscle (0.17 +/- 0.10). Localized MRI spectra gave a large part of the signal originating from fat protons, but with a significant percentage from water protons. At light and electron microscopy the lipid deposition appeared to be composed of low-density material filling a large part of the cytoplasm, and the porphyrin aggregates were easily recognizable. The data demonstrate that an in vivo study of the HG was feasible and that high-field MRI allowed analysis of the gross anatomy detecting the lipid content of the gland.

Dynamic contrast-enhanced magnetic resonance imaging of the sarcopenic muscle.

BACKGROUND: Studies about capillarity of the aged muscle provided conflicting results and no data are currently available about the magnetic resonance imaging (MRI) in vivo characteristics of the microvascular bed in aged rats. We have studied age-related modifications of the skeletal muscle by in vivo T2-relaxometry and dynamic contrast-enhanced magnetic resonance imaging (CE-MRI) at high field intensity (4.7 T). The aim of the work was to test the hypothesis that the ageing process involves microvessels in skeletal muscle. METHODS: The study was performed in 4-month-old (n = 6) and 20-month-old (n = 6) rats. RESULTS: At MRI examination, the relaxation time T2 of the gastrocnemius muscle showed no significant difference between these two groups. The kinetic of contrast penetration in the tissue showed that in 4-month-old rats the enhancement values of the signal intensity at different time-points were significantly higher than those found in senescent rats. CONCLUSION: The reported finding suggests that there is a modification of the microcirculatory function in skeletal muscle of aged rats. This work also demonstrates that CE-MRI allows for an in vivo quantification of the multiple biological processes involving the skeletal muscle during aging. Therefore, CE-MRI could represent a further tool for the follow up of tissue modification and therapeutic intervention both in patients with sarcopenia and in experimental models of this pathology.

Regional changes in the contralateral "healthy" hemisphere after ischemic lesions evaluated by quantitative T2 parametric maps.

Modifications in the contralateral "healthy" hemisphere in a population of rats bearing cortical infarction were studied in vivo by magnetic resonance imaging (MRI) with the aim to investigate whether cerebral areas not directly involved in the lesion react at the presence of an ischemic lesion. The study was performed in rats in which a transtemporal approach was adopted to occlude the right middle cerebral artery (MCA). For MRI, the animals were examined at 4.7 Tesla and quantitative T2 parametric images were obtained by a multiecho sequence. Healthy rats and sham-operated animals were used as control groups. The quantitative T2 parametric images showed that in the first week after the ischemia a significant increase in the mean T2 was seen in the lesioned parietal cortex, compared to the corresponding region of healthy rats (106 msec vs. 68 msec, P < 0.001). The contralateral "healthy" hemisphere showed T2 mean values not significantly different from the corresponding hemisphere of healthy rats (71 msec vs. 70 msec). However, a statistically significant increase in the T2 values was evident in the hypothalamic region (74 msec vs. 66 msec, P < 0.001). In rats examined 1 month after the ischemia, the T2 values of the hypothalamus were lower than those observed one week after ischemia (69 msec) but remained higher than in controls. The present study demonstrates that after a cerebral ischemia areas of secondary involvement distant from the lesion are present and can be studied in vivo by quantitative MRI.