MR evaluation of vessel size imaging of human gliomas: Validation by histopathology.

PURPOSE: To compare the vessel size and the cerebral blood volume in human gliomas with histopathology. Vessel size imaging (VSI) is a dynamic susceptibility contrast method for the assessment of the vessel size in normal and pathological tissue. Previous publications in rodents showed a satisfactory conformity with the vessel size derived from histopathology. To assess the clinical value, further, the progression-free interval was determined and correlated. MATERIALS AND METHODS: Twenty-five gliomas (WHO grade °II [n = 10], °III [n = 3], °IV [n = 12]) were prospectively included and received a stereotaxic biopsy after VSI. The vessel size and the cerebral blood volume (CBV) were calculated in regions of interest at the tumor edge and correlated with the vessel size measured by histopathology. RESULTS: Both VSI and CBV showed a good correlation with the vessel size in histopathology (up to r = 0.84, P < 0.001, and r = 0.62, P < 0.001, respectively). Slope and offset of the linear regression (y = 0.77x + 0.36 µm) suggest that the size of normal capillaries is overestimated with VSI, while for grossly enlarged vessels an underestimation occurs. Both VSI and CBV were negatively correlated with the progression-free interval (r = -0.57, P = 0.008, and r = -0.50, P = 0.025, respectively). CONCLUSION: The correlation between VSI and vessel size from histopathology is in good accordance with the animal studies. The overestimation of small capillary sizes is also known from the animal trials. Vessel size and CBV showed similar results, both for the correlation with the histopathological vessel size and the progression-free interval.

[New therapies for interventional cardiovascular magnetic resonance imaging]. / Interventionelle kardiovaskuläre Magnetresonanz: neue therapeutische Anwendungen.

Interventional cardiovascular magnetic resonance (iCMR) makes new minimally invasive therapies possible and is an attractive alternative option with high soft-tissue contrast and the possibility of a three-dimensional MR angiography compared to conventional angiography-guided interventions. Interventional MR-navigated cardiovascular therapies represent a new discipline whose systematic development will foster minimally invasive interventional procedures without radiation exposure. MR-compatible endovascular catheters and guide wires are needed for delivery of devices and therapies. Catheter tracking is based on active and passive approaches. Currently performed MR-guided cardiovascular procedures have been used to monitor, navigate and track endovascular catheters and to deliver local therapies to the targets. Heating of endovascular MR catheters, guide wires and devices during imaging still presents high safety risks. Cardiovascular MR contrast media improve the capability of MRI by enhancing blood signal, pathologic targets (such as myocardial infarctions and atherosclerotic plaques) and tracking injected therapies (such as cells or genes). Labeling injected therapies or cells with MR contrast media leads interventionalists to trace the distribution, differentiation and survival. The requirements for this iCMR technique are (1) high spatial and temporal resolution imaging, (2) special catheters and devices, and (3) effective therapeutic drugs. This review summarizes current aspects of iCMR, provides examples of its use in the heart and beyond, discusses the infrastructure required for successful implementation of iCMR approaches, and outlines the challenges that must be overcome for iCMR to advance further.

An overview on the advances in cardiovascular interventional MR imaging.

Interventional cardiovascular magnetic resonance imaging (iCMR) represents a new discipline whose systematic development will foster minimally invasive interventional procedures without radiation exposure. New generations of open, wide and short bore MR scanners and real time sequences made cardiovascular intervention possible. MR compatible endovascular catheters and guide-wires are needed for delivery of devices such as stents or atrial septal defect (ASD) closures. Catheter tracking is based on active and passive approaches. Currently performed MR-guided procedures are used to monitor, navigate and track endovascular catheters and to deliver local therapeutic agents to targets, such as infarcted myocardium and vascular walls. Heating of endovascular MR catheters, guide-wires and devices during imaging still presents high safety risks. MR contrast media improve the capabilities of MR imaging by enhancing blood signal, pathologic targets (such as myocardial infarctions and atherosclerotic plaques), endovascular catheters and by tracking injected therapeutic agents. Labeling injected soluble therapeutic agents, genes or cells with MR contrast media enables interventionalists to ensure the administration of the drugs in the target and to trace their distribution in the targets. The future clinical use of this iCMR technique requires (1) high spatial and temporal resolution imaging, (2) special catheters and devices and (3) effective therapeutic agents, genes or cells. These conditions are available at a low scale at the present time and need to be developed in the near future. Such progress will lead to improved patient care and minimize invasiveness.

Cell labeling with the positive MR contrast agent Gadofluorine M.

The purpose of this study was to label human monocytes with Gadofluorine M by simple incubation for subsequent cell depiction at 1.5 and 3 T. Gadofluorine M displays a high r(1) relaxivity and is spontaneously phagocytosed by macrophages. Human monocytes were incubated with Gadofluorine M-Cy at varying concentrations and incubation times and underwent MR imaging at 1.5 and 3 T at increasing time intervals after the labeling procedure. R1-relaxation rates and r1 relaxivities of the labeled cells and non-labeled controls were determined. Cellular contrast agent uptake was examined by fluorescence microscopy and quantified by ICP-AES. Efficient cell labeling was achieved after incubation of the cells with 25 mM Gd Gadofluorine M for 12 h, resulting in a maximal uptake of 0.3 fmol Gd/cell without impairment of cell viability. Fluorescence microscopy confirmed internalization of the fluorescent contrast agent by monocytes. The r1 relaxivity of the labeled cells was 137 mM(-1)s(-1) at 1.5 T and 80.46 mM(-1)s(-1) at 3 T. Imaging studies showed stable labeling for at least 7 days. Human monocytes can be effectively labeled for MR imaging with Gadofluorine M. Potential in vivo cell-tracking applications include targeting of inflammatory processes with Gadofluorine-labeled leukocytes or monitoring of stem cell therapies for the treatment of arthritis.

MR imaging of antigen-induced arthritis with a new, folate receptor-targeted contrast agent.

The purpose of this study was to investigate if the new folate receptor-targeted Gd-chelate P866 may enhance immune-mediated arthritis. A monoarthritis was induced in the right knee of 15 Sprague-Dawley rats. MR imaging of both knees was performed at 2 T before and up to 2 h and 24 h after injection (p.i.) of P866 (n = 3 dose finding study and n = 6, 0.02 mmol Gd/kg), the non-FR targeted P866 analog P1001 (n = 3 at 24 h after P866-administration, 0.02 mmol Gd/kg) or Gd-DOTA (n = 6, 0.1 mmol Gd/kg). Pulse sequences comprised T(1)-SPGR 80 degrees /50 ms/1.7 ms (flip angle/TR/TE) and inversion recovery 10 degrees /3000 ms/1500 ms/50-3050, 10 000 ms (flip angle/TR/TE/TI) sequences. DeltaSI-data and T(1)-relaxation times of arthritic knees and contralateral normal knees were determined. Folate receptor expression was confirmed with histopathology. All three contrast agents showed an initial perfusion effect with significantly higher DeltaSI-data of arthritic knees compared with normal knees (p < 0.05). In addition, P866, but not P1001 or Gd-DOTA, showed a prolonged enhancement of the synovitis. Compared with precontrast values, the T(1)-relaxation times of inflamed synovia were significantly decreased at 2 h p.i. of P866 (p < 0.05), but not P1001 or Gd-DOTA (p > 0.05). Histopathology confirmed the presence of folate receptors in the inflamed joints, but not normal joints. Thus, results suggest a specific accumulation of the folate receptor-targeted Gd-chelate P866 in this arthritis model.

Optical imaging of experimental arthritis using allogeneic leukocytes labeled with a near-infrared fluorescent probe.

PURPOSE: The purpose of this study was to assess the feasibility of inflammation detection in an antigen-induced arthritis model using fluorescent leukocytes and optical imaging. METHODS: Antigen-mediated monoarthritis was induced in the right knee of 12 Sprague-Dawley rats. Six rats remained untreated and six rats were treated with cortisone. All rats received ex vivo fluorescent-labeled rat leukocytes. Optical images of both knees were acquired before and at 5 min, 1 h, 4 h, and 24 h after cell injection. Images were evaluated qualitatively and quantitatively by calculating signal intensity ratios between the right arthritic (A) and contralateral normal (N) knee. A/N ratios were tested for significant differences between baseline values and values after cell injection using a paired t test as well as between the untreated and cortisone-treated group using an unpaired t test. Synovial specimens were processed and evaluated for labeled cells with fluorescence microscopy. RESULTS: At 4 h and 24 h p.i., the A/N ratios of untreated arthritic knees showed a significant signal increase compared with baseline values (p<0.05) and a significant difference compared with A/N ratios of cortisone-treated animals (p<0.05). Fluorescent microscopy confirmed the presence of labeled cells in the arthritic synovium. CONCLUSION: Inflammation in antigen-induced arthritis can be detected with ex vivo labeled allogenic leukocytes and optical imaging.