Free-breathing renal MR angiography with steady-state free-precession (SSFP) and slab-selective spin inversion: initial results.

BACKGROUND: The aim of our study was the investigation of a novel navigator-gated three-dimensional (3D) steady-state free-precession (SSFP) sequence for free-breathing renal magnetic resonance angiography (MRA) without contrast medium, and to examine the advantage of an additional inversion prepulse for improved contrast. METHODS: Eight healthy volunteers (mean age 29 years) and eight patients (mean age 53 years) were investigated on a 1.5 Tesla MR system (ACS-NT, Philips, Best, The Netherlands). Renal MRA was performed using three navigator-gated free-breathing cardiac-triggered 3D SSFP sequences [repetition time (TR) = 4.4 ms, echo time (TE) = 2.2 ms, flip angle 85 degrees, spatial resolution 1.25 x 1.25 x 4.0 mm(3), scanning time approximately 1 minute 30 seconds]. The same sequence was performed without magnetization preparation, with a non-slab selective and a slab-selective inversion prepulse. Signal-to-noise ratio (SNR), contrast-to-noise (CNR) vessel length, and subjective image quality were compared. RESULTS: Three-dimensional SSFP imaging combined with a slab-selective inversion prepulse enabled selective and high contrast visualization of the renal arteries, including the more distal branches. Standard SSFP imaging without magnetization preparation demonstrated overlay by veins and renal parenchyma. A non-slab-selective prepulse abolished vessel visualization. CNR in SSFP with slab-selective inversion was 43.6 versus 10.6 (SSFP without magnetization preparation) and 0.4 (SSFP with non-slab-selective inversion), P < 0.008. CONCLUSION: Navigator-gated free-breathing cardiac-triggered 3D SSFP imaging combined with a slab-selective inversion prepulse is a novel, fast renal MRA technique without the need for contrast media.

Free-breathing 3D steady-state free precession coronary MR angiography with radial k-space sampling: comparison with cartesian k-space sampling and cartesian gradient-echo coronary MR angiography--pilot study.

The authors compared radial steady-state free precession (SSFP) coronary magnetic resonance (MR) angiography, cartesian k-space sampling SSFP coronary MR angiography, and gradient-echo coronary MR angiography in 16 healthy adults and four pilot study patients. Standard gradient-echo MR imaging with a T2 preparatory pulse and cartesian k-space sampling was the reference technique. Image quality was compared by using subjective motion artifact level and objective contrast-to-noise ratio and vessel sharpness. Radial SSFP, compared with cartesian SSFP and gradient-echo MR angiography, resulted in reduced motion artifacts and superior vessel sharpness. Cartesian SSFP resulted in increased motion artifacts (P <.05). Contrast-to-noise ratio with radial SSFP was lower than that with cartesian SSFP and similar to that with the reference technique. Radial SSFP coronary MR angiography appears preferable because of improved definition of vessel borders.

A phase I pharmacokinetic study of hypoxic abdominal stop-flow perfusion with gemcitabine in patients with advanced pancreatic cancer and refractory malignant ascites

PURPOSE: As no curative treatment for advanced pancreatic and biliary cancer with malignant ascites exists, new modalities possibly improving the response to available chemotherapies must be explored. This phase I study assesses the feasibility, tolerability and pharmacokinetics of a regional treatment of gemcitabine administered in escalating doses by the stop-flow approach to patients with advanced abdominal malignancies (adenocarcinoma of the pancreas, n = 8, and cholangiocarcinoma of the liver, n = 1). EXPERIMENTAL DESIGN: Gemcitabine at 500, 750 and 1,125 mg/m(2) was administered to three patients at each dose level by loco-regional chemotherapy, using hypoxic abdominal stop-flow perfusion. This was achieved by an aorto-caval occlusion by balloon catheters connected to an extracorporeal circuit. Gemcitabine and its main metabolite 2',2'-difluorodeoxyuridine (dFdU) concentrations were measured by high performance liquid chromatography with UV detection in the extracorporeal circuit during the 20 min of stop-flow perfusion, and in peripheral plasma for 420 min. Blood gases were monitored during the stop-flow perfusion and hypoxia was considered stringent if two of the following endpoints were met: pH </= 7.2, pO(2) nadir ratio </=0.70 or pCO(2) peak ratio >/=1.35. The tolerability of this procedure was also assessed. RESULTS: Stringent hypoxia was achieved in four patients. Very high levels of gemcitabine were rapidly reached in the extracorporeal circuit during the 20 min of stop-flow perfusion, with C (max) levels in the abdominal circuit of 246 (+/-37%), 2,039 (+/-77%) and 4,780 (+/-7.3%) mug/ml for the three dose levels 500, 750 and 1,125 mg/m(2), respectively. These C (max) were between 13 (+/-51%) and 290 (+/-12%) times higher than those measured in the peripheral plasma. Similarly, the abdominal exposure to gemcitabine, calculated as AUC(t0-20), was between 5.5 (+/-43%) and 200 (+/-66%)-fold higher than the systemic exposure. Loco-regional exposure to gemcitabine was statistically higher in presence of stringent hypoxia (P < 0.01 for C (max) and AUC(t0-20), both normalised to the gemcitabine dose). Toxicities were acceptable considering the complexity of the procedure and were mostly hepatic; it was not possible to differentiate the respective contributions of systemic and regional exposures. A significant correlation (P < 0.05) was found between systemic C (max) of gemcitabine and the nadir of both leucocytes and neutrophils. CONCLUSIONS: Regional exposure to gemcitabine-the current standard drug for advanced adenocarcinoma of the pancreas-can be markedly enhanced using an optimised hypoxic stop-flow perfusion technique, with acceptable toxicities up to a dose of 1,125 mg/m(2). However, the activity of gemcitabine under hypoxic conditions is not as firmly established as that of other drugs such as mitomycin C, melphalan or tirapazamine. Further studies of this investigational modality, but with bioreductive drugs, are therefore warranted first to evaluate the tolerance in a phase I study and later on to assess whether it does improve the response to chemotherapy.

Assessment of systolic and diastolic LV function by MR myocardial tagging.

Heart failure has been divided into several different forms depending on etiology, clinical course and pathophysiology of left ventricular (LV) dysfunction. Systolic and diastolic dysfunction are characterized by a reduced cardiac output with normal (= diastolic dysfunction) or depressed (= systolic dysfunction) LV pump function. New diagnostic techniques such as magnetic resonance imaging (MRI) allow to determine noninvasively LV 3D motion by labelling specific myocardial regions (= myocardial "tagging") with a rectangular or radial grid. From the deformation of this grid rotational and translational motion of the heart can be derived. A "wringing" motion of the left ventricle has been described during systole which includes a clockwise rotation at the base and a counterclockwise rotation at the apex. During diastole, an "untwisting" motion has been demonstrated. In the normal heart, diastolic "untwisting" occurs primarily during isovolumic relaxation, analogous to the systolic "wringing" which takes place mainly during isovolumic contraction. A prolongation of the "untwisting" motion was found in the hypertrophied (aortic stenosis) and hibernating myocardium. Thus, heart failure is associated with profound alterations in the mechanical function of the heart which are manifested by changes in systolic "wringing" and diastolic "untwisting" motion.

Distribution of free and liposomal doxorubicin after isolated lung perfusion in a sarcoma model.

BACKGROUND: Isolated lung perfusion (ILP) with free and a novel liposomal-encapsulated doxorubicin (Liporubicin, CT Sciences SA, Lausanne, Switzerland) was compared with respect to drug uptake and distribution in rat lungs bearing a sarcomatous tumor. METHODS: A single sarcomatous tumor was generated in the left lung of 39 Fischer rats, followed 10 days later by left-sided ILP (n = 36) with free and equimolar-dosed liposomal doxorubicin at doses of 100 microg (n = 9) and 400 microg (n = 9) for each doxorubicin formulation. In each perfused lung, the drug concentration and distribution were assessed in the tumor and in three areas of normal lung parenchyma by high-performance liquid chromatography (n = 6) and fluorescence microscopy (n = 3). Histologic assessment and immunostaining with von Willebrand factor was performed in 3 animals with untreated tumors. RESULTS: The sarcomatous tumors in controls were well vascularized with fine branching capillaries present throughout the tumors. Isolated lung perfusion resulted in a heterogeneous drug distribution within the perfused lung and a consistently lower drug uptake in tumors than in lung parenchyma for both doxorubicin formulations and both drug doses applied. Isolated lung perfusion with free doxorubicin resulted in a significantly higher drug uptake than Liporubicin in both the tumor and lung tissue for both drug doses applied (p < 0.01). However, the tumor/normal tissue drug ratio was lower for free than for liposomal doxorubicin at a drug dose of 100 microg (0.27 +/- 0.1 vs 0.53 +/- 0.5; p = 0.225) and similar for both doxorubicin formulations at a drug dose of 400 microg (0.67 +/- 0.2 vs 0.54 +/- 0.2; p = 0.335). Both doxorubicin formulations resulted in fluorescence signaling emerging from all tissue compartments of normal lung parenchyma but only in weak and sporadic signaling from the tumors confined to the tumor periphery and vessels situated within the tumor for both drug doses assessed. CONCLUSIONS: Isolated lung perfusion with free and liposomal doxorubicin resulted in a heterogeneous drug distribution within the perfused lung and in a lower drug uptake in tumors than in lung tissue for both doxorubicin formulations and drug doses applied.

Measuring brain perfusion with intravoxel incoherent motion (IVIM): Initial clinical experience.

PURPOSE: To evaluate the feasibility of intravoxel incoherent motion (IVIM) perfusion measurements in the brain with currently available imaging systems. MATERIALS AND METHODS: We acquired high in-plane resolution (1.2 × 1.2 mm(2) ) diffusion-weighted images with 16 different values of b ranging from 0 to 900 s/mm(2) , in three orthogonal directions, on 3T systems with a 32-multichannel receiver head coil. IVIM perfusion maps were extracted by fitting a double exponential model of signal amplitude decay. Regions of interest were drawn in pathological and control regions, where IVIM perfusion parameters were compared to the corresponding dynamic susceptibility contrast (DSC) parameters. RESULTS: Hyperperfusion was found in the nonnecrotic or cystic part of two histologically proven glioblastoma multiforme and in two histologically proven glioma WHO grade III, as well as in a brain metastasis of lung adenocarcinoma, in a large meningioma, and in a case of ictal hyperperfusion. A monoexponential decay was found in a territory of acute ischemia, as well as in the necrotic part of a glioblastoma. The IVIM perfusion fraction f correlated well with DSC CBV. CONCLUSION: Our initial report suggests that high-resolution brain perfusion imaging is feasible with IVIM in the current clinical setting. J. Magn. Reson. Imaging 2014;39:624-632. © 2013 Wiley Periodicals, Inc.

p53 status correlates with histopathological response in patients with soft tissue sarcomas treated using isolated limb perfusion with TNF-alpha and melphalan.

BACKGROUND: Recombinant tumor necrosis factor-alpha (TNF-alpha) combined to melphalan is clinically administered through isolated limb perfusion (ILP) for regionally advanced soft tissue sarcomas of the limbs. In preclinical studies, wild-type p53 gene is involved in the regulation of cytotoxic action of TNF-alpha and loss of p53 function contributes to the resistance of tumour cells to TNF-alpha. The relationship between p53 status and response to TNF-alpha and melphalan in patients undergoing ILP is unknown. PATIENTS AND METHODS: We studied 110 cases of unresectable limbs sarcomas treated by ILP. Immunohistochemistry was carried out using DO7mAb, which reacts with an antigenic determinant from the N-terminal region of both the wild-type and mutant forms of the p53 protein, and PAb1620mAb, which reacts with the 1620 epitope characteristic of the wild-type native conformation of the p53 protein. The immunohistochemistry data were then correlated with various clinical parameters. RESULTS: P53DO7 was found expressed at high levels in 28 patients, whereas PAb1620 was negative in 20. The tumours with poor histological response to ILP with TNF-alpha and melphalan showed significantly higher levels of p53-mutated protein. CONCLUSIONS: Our results might be a clue to a role of p53 protein status in TNF-alpha and melphalan response in clinical use.

Cerebellar cortical layers: in vivo visualization with structural high-field-strength MR imaging.

Purpose: To perform in vivo imaging of the cerebellum with an in-plane resolution of 120 mm to observe its cortical granular and molecular layers by taking advantage of the high signal-to-noise ratio and the increased magnetic susceptibility-related contrast available at high magnetic field strength such as 7 T. Materials and Methods: The study was approved by the institutional review board, and all patients provided written consent. Three healthy persons (two men, one woman; mean age, 30 years; age range, 28-31 years) underwent MR imaging with a 7-T system. Gradient-echo images (repetition time msec/echo time msec, 1000/25) of the human cerebellum were acquired with a nominal in-plane resolution of approximately 120 mum and a section thickness of 1 mm. Results: Structures with dimensions as small as 240 mum, such as the granular and molecular layers in the cerebellar cortex, were detected in vivo. The detection of these structures was confirmed by comparing the contrast obtained on T2*-weighted and phase images with that obtained on images of rat cerebellum acquired at 14 T with 30 mum in-plane resolution. Conclusion: In vivo cerebellar imaging at near-microscopic resolution is feasible at 7 T. Such detailed observation of an anatomic area that can be affected by a number of neurologic and psychiatric diseases, such as stroke, tumors, autism, and schizophrenia, could potentially provide newer markers for diagnosis and follow-up in patients with such pathologic conditions. (c) RSNA, 2010.

Hepatic hemangiomas : factors associated with T2 shine-through effect on diffusion-weighted MR sequences

Objectifs: Déterminer la fréquence et les facteurs prédictifs de l'effet T2 shine-through dans l'hémangiome hépatique. Matériels et méthodes: Entre janvier 2010 et novembre 2011, l'imagerie par résonance magnétique du foie de 149 patients avec 388 hémangiomes hépatiques a été revue rétrospectivement. Les caractéristiques lésionnelles: la taille, la localisation, le signal et l'aspect en T1, T2 et en diffusion, l'effet T2 shine-through, le coefficient apparent de diffusion des hémangiomes hépatiques et du foie et type de rehaussement ont été évalués. Résultats: L'effet T2 shine-through était observé dans 204/388 (52.6%) des hémangiomes hépatiques et 100 (67.1%) patients. L'ADC moyen des hémangiomas avec T2 shine-through effect était significativement plus bas que les hémangiomas sans T2 shine-through effect (2.0 +/- 0.48 vs 2.38 +/- 0.45 10"3 mm2/s, P < .0001). L'analyse multivariée retrouvait comme facteurs indépendants de la présence d'un effet T2 shine-through un hypersignal sur les images fat- suppressed T2-weighted fast spin-echo, les hémangiomes avec un rehaussement classique et retardé, et l'ADC du foie. Conclusion: Le T2 shine-through effect est fréquemment observé dans les hémangiomes hépatiques et dépend des caractéristiques lésionnelles. Sa présence ne remet pas en question le diagnostic lorsque les signes IRM typiques sont présents.