In vivo MRI follow-up of murine tumors treated by electrochemotherapy and other electroporation-based treatments.

In vivo cell electropermeabilization can be used alone or in combination with a hydrophilic, nonpermeant cytotoxic drug such as bleomycin (electrochemotherapy) to efficiently treat tumors. We used magnetic resonance imaging to detect rapid structural modifications in tumors treated by electroporation-based methods. Water diffusion coefficient (ADC), transverse relaxation time (T(2)) and tumor volume of fibrosarcomas xenografted on syngenic mice were measured upon 3 groups of 6 treated mice within the 48 hrs following ECT done with a normal (BE) or a high dose of bleomycin (HBE), and after irreversible electroporation (IRE), and in three control groups. As expected, the tumor volume increased in the control groups at 48 hrs (p < 0.05) and the values of ADC and T2 did not varied significantly in the control groups except for ADC decrease and T2 increase observed between 3 hrs and 24 hrs (p < 0.03) in the group that received bleomycin only. Tumor volumes decreased significantly at 24 hrs in the IRE and HBE groups. The mean tumor ADC increased significantly at 24 hrs (117.6%, p < 0.03) in the BE group, probably reflecting apoptosis, while in the HBE group the mean tumor ADC increased earlier, at 10 hrs (119%, p < 0.03) because of the speed of the pseudoapopototic process. In the IRE group, the mean tumor ADC decreased significantly at 1 hrs (p < 0.05) and 3 hrs (p < 0.03), and T(2) decreased (p < 0.03), both probably reflecting cell swelling induced by the vascular lock. Thus ADC and T(2) changes in the treated tumors correlated with previous histological observations on the same tumor models. Noteworthy, ADC allowed the visualization of early and rapid changes in the treated tumors, when tumor volume monitoring was not yet able to detect any effect of the treatments.

[Exploration of exercise intolerance by 31P NMR spectroscopy of calf muscles coupled with MRI and ergometry]. / Exploration de l'intolérance à l'exercice par spectroscopie RMN du phosphore des muscles fléchisseurs plantaires.

One hundred patients presenting with exercise intolerance or rhabdomyolysis episodes have been examined successively by 31P Nuclear Magnetic Resonance Spectroscopy (MRS) of leg plantar flexor muscles with exercise test. In all cases a muscle biopsy was performed. At the end of investigations, diagnosis of a metabolic myopathy was made in 33 patients: glycogenolysis or glycolysis deficiency in 8 cases, mitochondrial myopathy in 24 cases and CPT II deficiency in one case. Muscular dystrophy or congenital myopathy were diagnosed in 6 cases. No precise etiology could be found in 30 patients with either high CK levels or muscle biopsy abnormalities. Seven patients had rhabdomyolysis related to excessive physical activities. Twenty-four patients had functional symptoms. The principal MRS parameters used for diagnosis were the values of intracellular pH at the end of exercise and the time constant of phosphocreatine resynthesis during recovery. Lack of acidosis after exercise was observed in all patients with blockade of glycogenolysis or glycolysis. A slowing in phosphocreatine resynthesis was found in 66 p.cent of patients with definite mitochondrial myopathy. The specificity of these parameters were respectively 92.4 p.cent and 85.5 p.cent for the two groups. In conclusion (31)P MRS allows the detection of muscular glycogenoses with a sensitivity close to 100 p.cent. However, its sensitivity was lower for the detection of mitochondrial myopathies, as is also known for the other in vivo metabolic investigations, reflecting the heterogeneity of expression of mitochondrial abnormalities in a given muscle. The integration of imaging in the examination protocol may help to orientate towards the diagnostic of a dystrophy in some patients.

A comparison of voluntary and electrically induced contractions by interleaved 1H- and 31P-NMRS in humans.

Skeletal muscle voluntary contractions (VC) and electrical stimulations (ES) were compared in eight healthy men. High-energy phosphates and myoglobin oxygenation were simultaneously monitored in the quadriceps by interleaved (1)H- and (31)P-NMR spectroscopy. For the VC protocol, subjects performed five or six bouts of 5 min with a workload increment of 10% of maximal voluntary torque (MVT) at each step. The ES protocol consisted of a 13-min exercise with a load corresponding to 10% MVT. For both protocols, exercise consisted of 6-s isometric contractions and 6-s rest cycles. For an identical mechanical level (10% MVT), ES induced larger changes than VC in the P(i)-to-phosphocreatine ratio [1.38 +/- 1.14 (ES) vs. 0.13 +/- 0.04 (VC)], pH [6.69 +/- 0.11 (ES) vs. 7.04 +/- 0.07 (VC)] and myoglobin desaturation [43 +/- 15.9 (ES) vs. 6.1 +/- 4.6% (VC)]. ES activated the muscle facing the NMR coil to a greater extent than did VCs when evaluated under identical technical conditions. This metabolic pattern can be interpreted in terms of specific temporal and spatial muscle cell recruitment. Furthermore, at identical levels of energy charge, the muscle was more acidotic and cytoplasm appeared more oxygenated during ES than during VC. These results are in accordance with a preferential recruitment of type II fibers and a relative muscle hyperperfusion during ES.

Fat suppression techniques in MRI: an update.

Due to short relaxation times, fat has a high signal on magnetic resonance images (MRI). This high signal, easily recognized on MRI, may be useful to characterize a lesion. However, small amounts of lipids are more difficult to detect on conventional MRI. In addition, the high signal due to fat may be responsible for artifacts such as ghosting and chemical shift. Lastly, a contrast enhancing tumor may be hidden by the surrounding fat. These problems have prompted development of fat suppression techniques in MRI. Fat may be suppressed on the basis of its difference in resonance frequency with water by means of frequency selective pulses or phase contrast techniques, or on the basis of its short T1 relaxation time by means of inversion recovery sequences. Lastly, hybrid techniques combining several of these fat suppression techniques are also possible. The aim of this paper is to review the basic principles of all these fat suppression techniques and to exemplify their clinical use.

Temperature changes induced in human muscle by radio-frequency H-1 decoupling: measurement with an MR imaging diffusion technique. Work in progress.

To investigate temperature increases in tissues during magnetic resonance (MR) imaging or spectroscopy, the authors measured temperature changes in vitro and in vivo (leg of a volunteer) in a condition simulating hydrogen-1 decoupling in MR spectroscopy. Noninvasive measurements were obtained by using the temperature dependence of the translational diffusion coefficient of water. Temperature was measured at 0.5 T (86 MHz) by using a stimulated-echo sequence that included intense gradient pulses and a procedure reducing sensitivity to bulk tissue motion. Calibration curves of the diffusion coefficient against thermocouple-measured temperature were obtained for a gelatin phantom and bovine muscle. Temperature changes were 5.3 degrees C +/- 0.5 at 2.5 cm from the coil in gelatin and 7.7 degrees C +/- 0.5 at 0.7 cm in bovine muscle. The temperature changed by 4.9 degrees C +/- 1.9 at 2.2 cm from the coil in the calf muscle of a volunteer. The H-1 decoupling protocol can be adapted (modifications in transmission power, duty cycle) to reduce heating effects to below safety recommendations.

Magnetic resonance imaging to monitor pathology of caudate-putamen after excitotoxin-induced neuronal loss in the nonhuman primate brain.

We used MR imaging to locate and monitor in vivo the pathological events taking place 2 to 4 weeks after unilateral striatal injections of ibotenic acid (IA) in the Papio papio baboon. As early as 2 weeks after IA injections, excitotoxic lesions in the caudate and the putamen were directly visualized on T1-weighted images as small areas of low signal intensity. On T2-weighted images, the lesion sites were visualized as areas of high-intensity signal, spreading over larger areas than the corresponding regions in T1-weighted images. These alterations of T2-values in the lesioned striatum persisted 4 weeks after surgery. However, as the striatal degeneration progressed from 2 to 4 weeks after lesion, the size of the areas of high signal intensity on T2-weighted images decreased, whereas the same regions appeared essentially unmodified on T1-weighted images. A marked enlargement of the ipsilateral lateral ventricle (a characteristic of excitotoxic striatal lesions) could be detected 4 weeks after surgery, on both axial T1- and T2-weighted images. Comparisons of MR images with postmortem anatomical data indicated that areas of increased T1 values corresponded to regions of severe neuronal depletion (a direct result of the excitotoxic lesion), whereas areas of increased T2 values corresponded to regions of increased content in astrocytes and ferritin and probably in the early period following lesion (2 weeks) to a superimposed edema.

In vivo MR spectroscopic imaging of the adrenal glands: distinction between adenomas and carcinomas larger than 15 mm based on lipid content.

The usefulness of MR spectroscopic imaging for discriminating between lipid and water was applied to the in vivo differentiation of adrenal adenomas from carcinomas. By using the Dixon sequence in 20 patients, the lipid content of 22 adrenal tumors larger than 15 mm was determined. The mean percentage of lipid in 15 adenomas was 13.4% (standard deviation, 8%), compared with 3.5% lipid (standard deviation, 2%) in seven carcinomas. Only one lesion would have been misclassified on the basis of in vivo measurements of lipid content. After surgery, in vitro MR spectroscopy was used to determine the percentage of lipid in excised samples of nine of the 22 tumors. These in vitro measurements confirmed the in vivo results on lesions larger than 20 mm in diameter. Respiratory artifacts appeared to decrease the accuracy of in vivo measurements in smaller lesions. In vivo MR spectroscopic imaging of adrenal tumors appears to be useful for differentiating between adrenal carcinomas and adenomas.

[Magnetic resonance imaging of the adrenal glands]. / l'Imagerie par résonance magnétique des glandes surrénales.

MRI is one of the most recent techniques of medical imaging. While it gives excellent results at the level of the skull, spine and pelvis, its use remains limited at thoracic and abdominal level because of movements which produce a deterioration in the image. However, the retroperitoneal space and in particular the adrenals may be explored under satisfactory conditions. The indications and results of this technique are discussed, based on the experience of adrenal examination in 90 cases.

[Magnetic resonance imaging in the diagnosis of adrenal pathology]. / Apport de l'I.R.M. au diagnostic en pathologie surrénalienne.

M.R.I. allows a good delineation of adrenals, due to the high contrast with fat and to the use of frontal planes. We showed on post operative adrenal lesions samples that the lipid percentages, high in normal and hyperplasic glands, was still high in most benign adenomas, and very low (under 5%) in adrenal carcinomas. MRI, with Dixon sequence, allows to evaluate this lipid percentage in adrenal lesions. Post-operative controls show a good agreement between in vivo and in vitro measurements. This simple technique should allow to discriminate between malignant and benign adrenal cortex lesions.

In vitro adrenal cortex lesions characterization by NMR spectroscopy.

Percentage of lipid content of 22 adrenal cortex lesions and their water proton longitudinal relaxation time were measured in vitro at 60 MHz. Although water relaxation times obtained on benign and malignant samples overlap each other, measurements of the percentage of lipids performed on the same tissues allow us to distinguish the two pathologies. The specific tool of characterization should be possible to obtain through in vivo spectroscopic imaging techniques.

[Demonstration by spectroscopy NMR at 1,5 Tesla of changes in lipid/water ratio in pathology of the adrenal cortex]. / Mise en évidence par spectroscopie RMN à 1,5 Tesla des changements de la proportion lipides/eau en pathologie du cortex surrénalien.

By NMR proton spectrometry with a main field of approximately 1.5 Tesla the authors have studied on pieces obtained at surgery changes of the lipid/water ratio in the cortex of diseased adrenal glands. On the basis of 58 samples taken from 20 different glands they show that this ratio is comparable in hyperplasias and adenomas but quite significantly reduced in carcinomas. They are therefore of the opinion that this ratio might serve as a malignancy index in spectroscopic imaging of patients bearing tumors of the adrenal cortex.