In vivo phosphorus magnetic resonance spectroscopy in multiple sclerosis.

Localized phosphorus magnetic resonance spectroscopy at 1.5 T was performed in 39 patients with multiple sclerosis and in 15 healthy controls. The multiple sclerosis spectra showed increased creatine phosphate levels. This increase was correlated with the severity of the handicap and was greater in patients with a progressive course of the disease than in patients with relapsing-remitting disease. No clear abnormalities were observed in the spectra of patients with multiple sclerosis regarding the phosphomonoesters, phosphodiesters, inorganic phosphate, and beta-adenosine triphosphate or with respect to pH values. There was an increased creatine phosphate level in the spectra in relation to a low metabolic state of the brain.

Tissue pH in cold-stored human donor livers preserved in University of Wisconsin solution. A noninavasive clinical study with 31P-magnetic resonance spectroscopy.

It is not known whether the tissue acidosis that accompanies cold storage is the beginning of irreversible cell injury, ultimately leading to cell death, or whether it is a natural "protective" mechanism for cells to survive hypoxic periods. To answer this question, the tissue pH of 45 cold-stored human donor livers preserved in University of Wisconsin solution (UW) was assessed shortly before implantation using noninvasive 31P magnetic resonance spectroscopy. We conclude that tissue pH during cold storage may be partly dependent upon hepatic glycogen stores and donor age. The wide range of tissue pH values that was observed at the time of implantation does not result in significant effects on cellular damage after transplantation. This indicates that tissue pH is not a major determinant for the viability of UW solution-preserved human donor livers, as indicated by postoperative hepatocellular damage and liver synthesis function. The membrane stabilizing and buffering capacity of UW solution appears to protect liver viability against tissue acidosis. Our results also indicate that liver tissue pH can be lower than has been previously assumed in the literature without significant adverse effects on liver viability.

Noninvasive metabolic assessment of human donor livers: prognostic value of 31P-magnetic resonance spectroscopy for early graft function.

BACKGROUND: The purpose of this study was to investigate whether phosphorus-31 magnetic resonance spectroscopy (31P-MRS) of the isolated donor liver can serve as a viability indicator with prognostic value for transplantation outcome. METHODS: Forty human donor livers preserved with University of Wisconsin solution were studied shortly before transplantation. The respective spectral peak areas of the isolated donor liver were correlated with the amount of hepatocellular graft damage and liver metabolic function shortly after implantation. RESULTS: The individual phosphomonoesters, inorganic phosphate, phosphodiesters, and nicotine adenine dinucleotide peaks were not prognostic for postoperative hepatocellular damage or liver metabolic capacity. The presence of adenosine triphosphate, however, predicts a significantly better metabolic capacity to eliminate bilirubin, to synthesize fibrinogen and antithrombin III, and to maintain a better prothrombin time after transplantation. Furthermore, this study is probably the first 31P-MRS demonstration in the human liver of phosphocreatine. CONCLUSIONS: In the clinical setting described, metabolic assessment using 31P-MRS did not result in a reliable noninvasive test to predict primary graft dysfunction. Study of the role of phosphocreatine in liver metabolism during cold storage is needed.

The tissue hydration state in UW-preserved human donor livers. A clinical study of the relation between proton magnetic resonance relaxation times, donor condition, preservation procedure, and early graft function.

To determine the relation between tissue hydration state--as indicated by tissue proton magnetic resonance relaxation times--in UW-preserved human donor livers and viability parameters of the donor and early graft function, "ex vivo" magnetic resonance relaxometry was performed with a clinical MR imaging system. Relaxometric data were obtained from MR images in which signal intensities were directly proportional to T1 and T2. Forty-three subsequently transplanted livers and five discarded livers were studied. The donor serum concentrations of direct and total bilirubin had a positive correlation with T1 (P < 0.05 and P < 0.01, respectively). Sequential measurements in 7 livers demonstrated a firm time relation between the cold storage time and the length of the relaxation times. As cold storage time lengthened, T1 and T2 shortened. T1 of the donor liver showed a significant negative correlation with recipient ASAT and ALAT values on days 1, 2, and 3 after transplantation. T1 in the discarded group was significantly higher than T1 in the accepted group. T2 was not different in the two groups. It is concluded that in UW-preserved human donor livers, the tissue hydration state, as indicated by the tissue MR relaxation times, is largely independent of the clinical condition of the organ donor and the preservation procedure. An optimum tissue hydration state, in UW-preserved donors liver might have protective properties against parenchymal damage, although the clinical consequences appear to be of minor importance. The capacity of relaxometry as a discriminative instrument to accept or to discard donor livers is poor.

Contribution of magnetic resonance spectroscopic imaging and L-[1-11C]tyrosine positron emission tomography to localization of cerebral gliomas for biopsy.

Proton magnetic resonance spectroscopic imaging (1H-MRSI) and positron emission tomography with the tracer L-[1-11C]tyrosine (11C-TYR) were used to localize gliomas for biopsy or resection. This is especially helpful in cases of low-grade gliomas, if these lesions are not visualized by contrast-enhanced computed tomographic and magnetic resonance imaging scans. The clues to improved localization are provided by changes in tissue metabolite contents, such as elevation of phosphocholine, indicating cellular proliferation; decrease of N-acetylaspartate, denoting loss of neurons (as these are replaced by tumor cells); and elevation of lactate, pointing to the prevalence of glycolysis, as observed in many tumors. These data on tissue metabolite content have been obtained in vivo in the patient by proton magnetic resonance spectroscopy; metabolite maps derived from these data then visualize the distribution of the various metabolites over the section of the brain under investigation. Alternatively, localization of a tumor may be achieved by means of positron emission tomography depicting the pattern of uptake of the amino acid tracer 11C-TYR, as it tends to be incorporated in the process of cellular proliferation and protein biosynthesis. Five cases are presented as examples.

Interpretation of nuclear magnetic resonance tomograms of the brain.

Nuclear magnetic resonance tomography is an imaging method based on the magnetic resonance behavior of protons, as they occur predominantly in tissue water or in fatty acids. This behavior, as characterized by the relaxation times T1 and T2, is determined by the chemical and physical environment of the protons. The relaxation properties of the tissue can be accentuated by selection of the appropriate pulse sequence. Interpretation of the images requires an understanding of the principles of the technique with which the relaxation times are expressed in the images, and acquaintance with the composition of the tissue in terms of relaxation properties (as in computerized tomography, tissue composition is expressed as attenuation coefficients).

Proton-nuclear magnetic resonance relaxation times in brain edema.

Proton relaxation times of protein solutions, bovine brain, and edematous feline brain tissue were studied as a function of water concentration, protein concentration, and temperature. In accordance with the fast proton exchange model for relaxation, a linear relation could be established between R1 and the inverse of the weight fraction of tissue water. This relation also applied to R2 of gray matter and of protein solutions. No straightforward relation with water content was found for R2 of white matter. Temperature-dependent studies indicated that in this case, the slow exchange model for relaxation had to be applied. The effect of macromolecules in physiological relevant concentrations on the total relaxation behavior of edematous tissue was weak. Total water content changes predominantly affected the relaxation rates. The linear relation may have high clinical potential for assessment of the status of cerebral edema on the basis of T1 and T2 readings from MR images.

Positron emission tomography study of 11C-acetoacetate uptake in a freezing lesion in cat brain, as correlated with 11C-tyrosine and 18F-fluorodeoxyglucose uptake, and with proton magnetic resonance imaging.

Using 11C-ACAC, 11C-TYR, and 18FDG as tracers, brain uptake of these substrates was studied in cat brain with a freezing lesion, by PET, at 1 day to 3 weeks after injury. Also MRI was conducted. Although the MRI scans depicted the morphological changes, such as edema formation, the PET studies of the brain uptake of substrates visualized the pattern of changes, which in the fresh lesion was largely governed by impairment of the BBB, but in the chronic lesion they were indicative of the proliferation of reactive cells in the process of tissue repair and edema resolution.

Optimization of scantiming in abdominal breathhold contrast-enhanced MRA: an empirical guideline.

The objective of this study to determine a suitable scan timing scheme in contrast enhanced MRA for the depiction of the arterial, the portal and the systemic venous system in the abdomen with maximum signal intensity in healthy subjects and in patients with cirrhosis. The signal intensity in the aorta, hepatic artery, portal vein, left renal vein and the supra- and infrarenal IVC were measured in 40 consecutive orthotopic liver transplantation candidates with cirrhosis and 20 healthy renal donors in a bolus triggered arterial scan and after 30, 60, 90 and 150 s respectively. The aorta and hepatic artery showed the highest signal intensity on the arterial scan. The portal and left renal vein showed the highest signal intensity after 30 s, the suprarenal IVC after 60 s and the infrarenal IVC after 90 s. No significant differences were found between healthy subjects and patients with cirrhosis. The arterial, portal and systemic venous system in the abdomen can be visualized selectively with maximum signal intensity by proper timing of the scans, hereby reducing redundant scans. Scanning at just the right time to achieve optimal vessel opacification can be promoted by using data from this study. The proposed scan scheme is suitable for subjects with and without cirrhosis.

Changes in 31P-relaxation times during organ preservation: observations on cold stored human donor livers.

During cold preservation for transplantation the tissue hydration state changes. It is not known whether such changes lead to altered relaxation times of 31P nuclei with potential consequences for the quantification of tissue metabolites. Therefore, 31P spectroscopic and proton T1 relaxometric measurements were performed on 42 isolated human donor livers shortly before implantation. The results demonstrate that 31P T1 relaxation times change during preservation for clinical transplantation, thus quantification of tissue metabolites in cold stored donor livers may be in part dependent on the tissue hydration state. Furthermore, it appeared that changes in tissue hydration state especially affect the physico-chemical characteristics of the intracellular fluid compartment. This study indicates that reliable spectroscopic quantification of tissue metabolites, particularly during sequential spectroscopic measurements in cold stored donor organs is best warranted under fully relaxed conditions.

Changes of relaxation times T1 and T2 in rat tissues after biopsy and fixation.

NMR spectroscopical measurements of relaxation times were conducted on muscle, intestine, fatty tissue and cerebral cortex and white matter of the rat at various time intervals following removal of the tissue. It appeared that most tissues can be stored at 4 degrees C up to 24 hours without noticeable effects on NMR relaxation parameters. Exceptions are the T2 of muscle and the T1 and T2 of intestine, which tended to change in the first hour after biopsy. Relaxation parameters change considerably after fixation of the tissues. Therefore the effects of fixation have to be taken into account when carrying out NMR measurements on fixed tissues.

Ex vivo MRI in extracorporeal liver surgery.

Extracorporeal resection of hepatic tumors that were considered inoperable in the past is now possible in selected cases. Such procedures require high-quality preoperative images for the exact delineation of the tumor extent and for an optimal planning of the line of parenchymal division. In-vivo CT and MRI can not always depict the tumor adequately. In such cases, ex-vivo MRI may be a useful additional technique. It combines a high spatial resolution with the best possible soft tissue contrast, as was learned from previous studies on donor livers destined for transplantation. Ex-vivo MRI favours both a sufficiently radical resection as well as sufficient hepatic functional reserve to be present for reimplantation. A case history is reported together with details on the technical procedure.

Comparison of contrast enhanced MR-angiography-MRI and digital subtraction angiography in the evaluation of pancreas and/or kidney transplantation patients: initial experience.

To evaluate whether combined contrast enhanced MRA and MRI (ce-MRA-MRI) has the potential to replace intra-arterial DSA (i.a.DSA) in patients with impaired graft function or suspected of vascular complications after pancreas and/or kidney transplantation. 7 patients after combined pancreas-kidney and 22 patients after kidney transplantation underwent ce-MRA-MRI and i.a.DSA within a 3 days interval. Qualitative and quantitative comparison of the arterial and venous supply, the parenchyma and urinary collecting system was made. Both ce-MRA and i.a.DSA showed good results in the detection of arterial stenoses. However, ce-MRA falsely suggested stenoses if vascular clips were used; on the other hand, i.a.DSA was less informative if the graft arteries were very tortuous. Ce-MRA was superior in depicting the venous anatomy (p < 0.001) and the parenchymal enhancement of the pancreatic grafts. For the assessment of the contrast excretion, the pyelocalyceal system and the ureter of the renal graft ce-MRA-MRI was superior (p < 0.001), for small caliber arteries in the renal grafts i.a.DSA was of greater value (p < 0.001). The combination of ce-MRA and MRI is reliable for evaluating the vascular anatomy and has several advantages over i.a.DSA after pancreas and/or kidney transplantation. It can replace i.a.DSA in patients with impaired graft function or suspected of vascular complications after pancreas and/or kidney transplantation.

Superior diagnostic strength of combined contrast enhanced MR-angiography and MR-imaging compared to intra-arterial DSA in liver transplantation candidates.

To evaluate the diagnostic value of combined contrast enhanced MRA (ce-MRA) and MRI compared to that of intra-arterial DSA (i.a.DSA) in liver transplantation, transjugular porto-systemic (TIPSS) and spleno-renal shunt candidates. 50 patients in the workup for liver transplantation underwent ce-MRA/MRI and i.a.DSA within a three days interval. Both examinations were assessed with respect to vessel anatomy and patency of the arterial, portal venous, porto-systemic collateral and systemic venous system. The results were compared with the intra-operative findings when available. Malignancy detection in ce-MRA/MRI and i.a.DSA were compared. There are no significant differences for the arterial part of the vascular supply to the liver that is important for transplantation. Although the differences for the portal system are not significant, the difference between the two techniques is of clinical importance because i.a.DSA failed to detect portal vein occlusion in 4 patients. Ce-MRA is significantly better for the detection of collaterals (p < 0.001) and the assessment of the inferior vena cava, the hepatic and the renal veins (p < 0.001). Although the detection of liver malignancy is poor in both techniques, ce-MRA/MRI is superior to i.a.DSA. This study shows that a one step diagnostic approach with a combination of ce-MRA and MRI is a valuable radiological tool with a superior diagnostic strength compared to i.a.DSA in the liver transplantation and shunt candidate. Therefore, ce-MRA/MRI should replace i.a.DSA in these patients groups.

Multi-exponential relaxation analysis with MR imaging and NMR spectroscopy using fat-water systems.

This study was undertaken to evaluate the feasibility of multiexponential relaxation data analysis to MR imaging techniques. The first part of this study contains accurate relaxation time measurements performed on a conventional spectrometer. In the second part, essentially the same measuring techniques were applied but now on standard whole body MR imaging equipment. T2 relaxation was measured using multi-echo techniques, T1 relaxation using multiple inversion recovery measurements. Manganese chloride solutions were used for verification of the single exponential model. Water and fat mixtures were considered for multi-exponentiality. Pure fat showed an intrinsic two-exponentiality in T1 and T2 relaxation. Mixtures of fat and water were analyzed and could at best be characterized by two exponentials, although at least three exponentials were known to be present. From the two-exponential fit the relative amounts of fat and water were calculated and compared with the mixture composition. Statistical criteria are discussed to discriminate between single and double exponential behavior in relaxation curves. It is concluded that the time consuming IR measurements for the determination of multiple T1 relaxation are not applicable in a clinical environment. Multiple T2 relaxation can be determined in a reasonable amount of time using multiple echo measurements in one image acquisition. It is shown that the observed values of T1 and T2 from tissues with intrinsic multiexponential relaxation behavior, measured with MR imaging or MR relaxation techniques on a whole-body imager or a conventional spectrometer, depend strongly on the way the experiments are set up and on the model accepted for data analysis.

Abdominal applications of fast MR imaging: a comparison of fast field echo (FFE) and spin echo (SE) pulse sequences.

Fast gradient echo (GE) MR imaging during breathhold was performed in 73 abdominal MR examinations in order to determine the value of GE technique in the reduction of movement artefacts and improvement of image quality. The results were compared with conventional spin-echo (SE) technique. T1-weighted SE images consistently demonstrated normal anatomy and pathology. T2*-weighted and intermediate GE technique proved to be superior to T2-weighted SE technique in a considerable number of cases providing not only better delineation of normal structures but also better lesion detection. At this stage GE technique should be considered as an adjunct to T1-weighted SE technique. If the artefacts presently inherent to GE imaging could be reduced or compensated for, this technique of rapid MR imaging during suspended respiration could become an important tool being one of the fastest techniques for abdominal MR imaging.

Proton spin relaxation studies of fatty tissue and cerebral white matter.

Proton spin longitudinal (T1) and transverse (T2) relaxation and proton density studies were carried out on human fatty tissue and bovine white matter, both in the native state and after immersion in D2O. It is concluded that nuclear magnetic resonance signals from fatty tissue result mainly from methyl and methylene protons of hydrocarbons. No contribution from lipid protons could be detected for white matter, although it contains a high percentage of lipids. Imaging experiments, resulting in T1, T2, and proton density maps, support the results obtained with spectroscopic relaxation studies.

Cystic lesions of the brain. A classification based on pathogenesis, with consideration of histological and radiological features.

A classification of the existing multitude of cystic lesions of the brain is proposed, which allows an understanding of their genesis and consequent therapeutic implications, as well as their diagnostic characteristics. Essentially, cerebral cystic lesions may be classified into the following categories: Cysts containing CSF-like fluid, which include ex vacuo type cysts, such as leptomeningeal cysts, and cysts following surgical resection; cysts with fluid secreting walls and CSF-like content, such as arachnoid cysts; cysts associated with dysgenesis, for example Dandy-Walker cysts. The ex vacuo cysts increase craniospinal compliance, whereas the other cysts with CSF-like content do not; they are not per se expansive, however, although their occasional location along CSF pathways may cause obstruction and hydrocephalus. Another category includes cysts with a lining of non-neural epithelium like colloid cysts, epidermoid cysts, or craniopharyngiomas. They may increase in size and cause symptoms by compression, although not at the rate of tumour-associated cysts. The cysts associated with gliomas and other tumours have a pathogenesis bearing upon blood-brain barrier impairment and formation of vasogenic oedema. Finally, one may distinguish a category of cysts with infectious origin, such as brain abscesses and hydatid cysts. The cysts with CSF-like contents may be recognised by their magnetic resonance characteristics resembling those of CSF, whereas cysts containing proteinaceous fluid are associated with blood-brain barrier impairment and consequent contrast enhancement. The cysts with a lining of non-neural epithelium exhibit diverse properties of attenuation on computed tomography (CT) and magnetic resonance imaging (MRI), depending on the nature of their cyst contents.

Our approach towards developing a specific tumour-targeted MRI contrast agent for the brain.

This review presents various aspects of the technological development, and their assessment in the design of a contrast agent for MRI, tailored to visualise tumours in the brain. First, it was demonstrated that magnetite as a contrast agent exhibited a much stronger relaxivity than gadolinium. The prepared magnetite particles bound to dextran, were also shown to be of appropriate size by electron microscopy. After their intravenous injection into rats with blood-brain barrier disruption, the lesion was strongly enhanced by T2-shortening. Furthermore, monoclonal antibodies directed against small cell lung carcinoma, proved to be able to penetrate into tumours, which had been raised by implantation of the small cell lung carcinoma cells into the brains of nude rats. As to the essential step, it was demonstrated in vitro that magnetite particles coupled to monoclonal antibodies by the biotin-streptavidin binding, could be bound to the target cells of the antibody, changing the relaxation rates of the latter. Finally it could be shown in vitro that an alternative approach, using lymphocytes to be targeted to tumour cells, also proved feasible, in that these lymphocytes could be labelled with magnetite that had been incorporated into liposomes. Further developments will be the in vivo assessment of the acquired progress in experimental animals, before clinical application is warranted.

Interpretation of magnetic resonance images making use of in vitro examinations of spinal tissue.

T1 and T2 relaxation times were determined in vitro at 21 MHz (0.5 T) for a variety of spinal and paraspinal tissues. Intensity formulas for spin echo and inversion recovery sequences were derived and used to calculate the intensities of these tissues as they would appear in magnetic resonance images. The intensity was calculated as a function of various repetition, echo, and inversion times. It is shown that the combination of acquiring in vitro relaxation time values and calculating intensity as a function of pulse timings is useful to predict the parameter setting for optimal contrast between certain tissues without applying series of magnetic resonance images.