In vivo determination of multiexponential T2 relaxation in the brain of patients with multiple sclerosis

In vivo measurement of T2 relaxation times in multiple sclerosis (MS) lesions by magnetic resonance imaging (MRI) is potentially useful for the evaluation of the disease activity. Seven patients with definite MS were investigated over a period of three years (19 examinations), using a whole-body MRI scanner operating at 0.15 T with a specially designed high-power radio-frequency head coil. A modified CPMG sequence with a 180 degree pulse interval of TE = 6 msec and 128 echoes was used for the T2 relaxation measurement of the areas of increased signal (AIS) and white matter (WM). A biexponential T2 analysis of each pixel of the spin-echo images was computed. The T2 relaxation processes were found to be a monoexponential function in WM. The T2 relaxation times of apparently normal white matter in MS patients was significantly longer than in control subjects. The T2 relaxation curves of the AIS were found in most cases to fit a biexponential function characterized by a short and a long T2. T2 long relaxation times of AIS were spread out over a wide range (150-560 msec). The study of T2 long histograms shows that some AIS can be divided into two or three parts depending on the T2 long values. Each of these parts may correspond to a pathological process such as edema, demyelination and gliosis. Evolution of T2 relaxation times over a period of time cannot as yet be correlated with modifications in the clinical state.     

MRI of hepatic lymphoma

Thirteen patients with biopsy proven hepatic lymphoma (2 Hodgkin, 11 Non-Hodgkin) and a control group of 15 patients with hepatic metastases were analyzed quantitatively and qualitatively by MRI. Focal hepatic lymphoma was most reliably detected (eight of eight patients) and appeared hypointense relative to liver on T₁ weighted (CNR − 7.4 ± 2.3) and hyperintense on T₂ weighted (CNR + 8.4 ± 2.9) images. The mean T₁ and T₂ relaxation times of focal hepatic lymphoma (T₁ = 832 ± 234 msec, T₂ = 84 ± 16 ms) differed significantly from adjacent non-tumorous liver (T₁ = 420 ± 121 ms, T₂ = 51 ± 9 ms; p < 0.05), however CNR values and relaxation times were similar to those of hepatic metastases. Diffuse hepatic lymphoma (microscopic periportal infiltration) was undetectable by MRI in three patients by either morphologic features or quantitative criteria. A mixed pattern of hepatic lymphoma (focal lesions and diffuse infiltration) showed focal areas of slightly decreased signal intensity on T₁ weighted images (CNR = −1.7 ± 0.4) while T₂ weighted images revealed multiple regions of focal hyperintensity (CNR = +13.3 ± 8.4) superimposed on a diffusely hyperintense liver. Our experience demonstrates that either T₁ or T₂ weighted techniques are useful in detecting focal and that T₂ weighted techniques are useful in detecting mixed hepatic lymphoma. Conventional image derived relaxation time measurements and quantitative parameters were of no additional diagnostic value.     

In vivo estimation of relaxation processes in benign hyperplasia and carcinoma of the prostate gland by magnetic resonance imaging

Tissue characterization for separating malignant from benign tissue is a clinically very important potential of magnetic resonance imaging (MRI). In this study quantitative determination of T1- and T2-relaxation processes was accomplished in five healthy volunteers, 10 patients with benign hyperplasia of the prostate gland and eight patients with prostatic carcinoma. Histological verification was obtained in all the patients. The measurements were performed on a wholebody MR-scanner operating at 1.5 T using six inversion recovery sequences (TR = 4000 msec) for T1-determination and a 32 spin-echo sequence (TR = 3000 or 2000 msec) for T2-estimation. The T1-relaxation curves all appeared monoexponential, whereas the T2-curves in most cases showed a multiexponential behaviour. A considerable overlap of the relaxation curves was seen. Consequently, we found no statistically significant differences between the T1- or the T2-relaxation times of the three groups investigated. It is concluded that tissue characterization based on relaxation time measurements with MRI does not seem to have a clinically useful role in prostatic disease.     

A study of T1-weighted 31phosphorus MR-spectroscopy from patients with focal and diffuse liver disease.

³¹P-MR-Spectroscopy was performed in 28 patients with focal (n = 23) and diffuse (n = 5) liver disease and in 18 healthy volunteers. The spectra were obtained with a whole body scanner operating at 1.5 T by using a surface coil. To get T₁-weighted ³¹P-spectra a short TR of 600 msec was taken, because T₁-weighted spectra of focal liver disease were more significantly different from spectra from healthy volunteers than density weighted ones. The VOI from patients with focal superficial alterations showed a mean volume of 172 ml, with diffuse liver disease 196 ml, and from volunteers 158 ml. Focal tumors filled up the VOI on an average of 70%. This investigation demonstrated that PME/β-ATP- and PDE/β-ATP-ratios were sensitive indicators for focal liver disease. As a result of this study we could establish a significant increase of PME/β-ATP- (0.75 ± 0.30) and PDE/β-ATP-ratios (1.68 ± 0.62) in patients with superficial focal liver metastases (n = 19) compared to the control group (PME/β-ATP: 0.49 ± 0.17, PDE/β-ATP: 1.24 ± 0.24; t-test: p < 0.02). Patients with a hemangioma (n = 1), liver infarction (n = 1), empyema of gallbladder (n = 1) and a hepatic involvement by a malignant lymphoma (n = 1) showed a similar increase of PME/β-ATP and/or PDE/β-ATP. Up to now spectral changes seemed to be non-specific. The ratios of ³¹P metabolites of the cirrhoses (n = 4) and the fatty liver (n = 1) did not show any characteristic changes versus the volunteers.     

Differentiation of hepatic cavernous hemangioma from metastases by rare sequence MR imaging.

In this study, in order to differentiate cavernous hemangioma and hepatic metastases, rapid acquisition relaxation enhanced (RARE) sequence was used. First, in vivo measurements of T1, T2 relaxation times and proton density were obtained using T1, T2 calculation protocol (TOMIKON S50, 0.5T) and multipoint techniques. These measurements were made from regions of interest placed over the liver, spleen (because of similarity of relaxation time values between hepatic metastases and spleen) and cavernous hemangioma (HCH). Based on these intrinsic parameters, T2 curves signal intensity of three different tissues were constructed. At TE = 500 ms, the signal intensity of the liver and spleen has been near zero whereas in HCH, the signal intensity remained. As RARE sequence is very similar to spin echo (SE), by replacing effective TE(ETE) = 500 ms in the RARE equation, two dimensional contrast-to-noise ratio (CNR) contour plots were constructed demonstrating signal intensity contrast between liver-spleen, liver-Hemangioma for two different scan times (3 min, 7.5 s) and pulse timing. Then, optimal RARE factor and inter echo times were obtained in order to have maximum CNR between liver-Hemangioma and minimum CNR between liver-spleen. These optimal parameters were performed on ten normal and five persons with known HCH. Images showed that in both scan times (3 min, 7.5 s); the liver and spleen were suppressed whereas the HCH was enhanced. The image quality in the scan time of 3 min was better than the scan time of 7.5 s. Moreover, in this study, two different sequences were compared: i) Multi-slice single echo (MSSE) for T1 weighted image ii) RARE (ETE = 80 ms) for T2-weighted image. This comparison was done to show maximum CNR between liver-spleen (metastases) and to choose a better sequence for detecting metastases. CNR in the RARE sequence was more than in the MSSE sequence.     

Quantitative multivoxel proton chemical shift imaging of the breast

The study of focal pathology by single-voxel magnetic resonance spectroscopy (MRS) is hampered by the impossibility to study tissue heterogeneity or compare the metabolite signals in breast lesion directly to those in unaffected tissue. Multivoxel MRS studies, while potentially allowing for truly quantitative tissue characterization, have up to now also been far from quantitative with, for example, the signal-to-noise ratio of the choline (Cho) signal serving as measure of tumor activity. Shown in this study is that in a standard clinical setting with a regular 1.5-T magnetic resonance scanner, it is possible to perform quantitative multivoxel MRS. With the use of literature values for the T1 and T2 relaxation times of Cho and water in fibroglandular breast tissue and tumors, one can determine the concentrations of Cho in different tumor compartments and surrounding tissues in two brief multivoxel MRS measurements. This opens excellent perspectives to quantitative diagnostic and follow-up studies of focal pathology such as lesions suspected of breast cancer.     

Proton MR properties of lyophilized urine samples from normal and stone former individuals

Proton MR measurements were performed in lyophilized urine samples collected from 5 normals (N) and 5 idiopathic hypercalciuric recurrent stone formers (SF). T1 and T2 relaxation times were measured with a Bruker PC Multispec at 20 MHz and 37 degrees C in the lyophilized samples and in samples gradually rehydrated. Significantly (p less than 0.01) prolonged T1 and T2 relaxation times were measured after addition of water to the lyophilized samples. The relaxation time prolongation patterns were significantly different (p less than 0.01) for the two groups; the rehydration curves of the lyophilized urine samples from the SF group had relatively shorter lag than that of N group. In calculations of water compartmentalization for similar water content, significant (p less than 0.01) differences in the fraction of bound water (FB) were found between the two groups. These results may reflect differences in the macromolecular properties, contents, in the amount of water binding sites and/or in the water multilayer thickness between the two groups. These differences, expressed as changes of the relaxation times values may provide new diagnostic possibilities of different renal pathologies.     

Recovery process of respiratory muscle strength in patients following stroke: A Pilot Study

Objective: To determine the recovery process of respiratory muscle strength during 3 months following stroke, and to investigate the association of change in respiratory muscle strength and physical functions. Additionally, we compared respiratory muscle strength with those of healthy subjects. Method: In this prospective, observational study, 19 stroke patients and 19 healthy subjects were enrolled. Maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), motricity index, trunk control test, 6-minute walk test (6MWT) and functional independence measure were assessed at 1, 2, and 3 months from stroke onset in stroke patients. MIP and MEP were assessed at arbitrary times in healthy subjects. Repeated one-way analysis of variance with Bonferroni post-hoc test was used to compare the change in respiratory muscle strength in each period in stroke patients. Pearson''s correlation coefficient was computed for changes in respiratory muscle strength and physical functions. Student''s t-test was used to compare respiratory muscle strength between stroke patients at 3 months from onset and healthy subjects. Results: MIP was significantly increased at 3 months compared to 1 month. MEP was significantly increased in 2 months and 3 months, compared to 1 month. MIP changes associated with 6MWT changes. Compared to healthy subjects, MIP and MEP at 3 months were significantly lower in stroke patients. Conclusion: Respiratory muscle strength significantly increased during 3 months following stroke. However, the trend of recovery may be different. MIP changes may associated with walking endurance changes. During 3 months following stroke, respiratory muscle strength did not recover to healthy subjects.     

Liver imaging at 1.5 tesla: pulse sequence optimization based on improved measurement of tissue relaxation times

In order to predict the most sensitive MR imaging sequence for detecting liver metastases at 1.5 T, in vivo measurements of T1 and T2 relaxation times and proton density were obtained using multipoint techniques. Based on these measurements, two-dimensional contrast contour plots were constructed demonstrating signal intensity contrast between hepatic lesions and surrounding liver parenchyma for different pulse sequences and pulse timing parameters. The data predict that inversion recovery spin echo (IRSE) imaging should yield the greatest contrast between liver metastases and liver parenchyma at 1.5 T, followed by short tau inversion recovery (STIR) and spin-echo (SE) pulse sequences. T2-weighted SE images provided greater liver/lesion contrast than T1-weighted SE pulse sequences. Calculated T1, T2, and proton density values of the spleen were similar to those of hepatic metastatic lesions, indicating that the signal intensity of the spleen may be used as an internal standard to predict the signal intensity of hepatic metastases on T1- and T2-weighted images at 1.5 T.     

The measurement of extracellular water volumes in tissues by gadolinium modification of 1H-NMR spin lattice (T1) relaxation

The present studies were conducted in RIF-1, M5076 and Panc02 murine tumor models to compare extracellular water measurements made by 51Cr-EDTA dilution techniques and a new method which exploits the concentration dependent modification of 1H-NMR proton relaxation by Gadolinium-DTPA-dimethyl glucamine (Gd-DTPA-dimeg) in plasma and tissues. The time dependent changes in T1 modification in tissue and plasma were determined at various intervals after i.v. injection of 0.1 ml of 100 mM Gd-DTPA-dimeg and Gd concentrations determined from standard curves of Gd concentration dependent T1 modification of mouse plasma. Comparison of tissue and plasma Gd concentrations permitted the calculation of Gd-DTPA-dimeg distribution volumes. In unperturbed RIF-1, M5076 and Panc02 tumors, Gd-DTPA-dimeg distribution volumes determined by the T1 modification technique were similar to extracellular water spaces determined by 51Cr-EDTA dilution assays. In mouse liver, the 51Cr-EDTA assay resulted in artifactually high extracellular water space estimates due to internalization of the probe; Gd-DTPA-dimeg distribution volumes determined in liver with both the 153Gd-DTPA-dimeg and by the T1 modification method were approximately 150 ul/gram. The Gd-DTPA-dimeg T1 modification method also provided good approximations of changes in extracellular water volumes in RIF-1 tumors after dexamethasone and cyclophosphamide treatments. These results indicate that Gd-DTPA-dimeg modification of proton relaxation may be extremely useful for monitoring changes in tumor water dynamics during cancer therapy.     

High-resolution study of nuclear magnetic relaxation dispersion of purine nucleotides: effects of spin-spin coupling

By combining magnetic field cycling in the range from 0.1mT to 7T with high-resolution NMR detection the T(1) relaxation dispersion (nuclear magnetic relaxation dispersion (NMRD)) of protons in the nucleotides adenosine mono-phosphate and guanosine mono-phosphate was measured in a site-specific way. While at high field the individual spins have distinctly different T(1) times, their scalar spin-spin interaction fulfills at low field the condition of strong coupling and leads to convergence of their T(1) dispersion curves. In addition, the spin-spin coupling can lead to oscillatory components in the relaxation kinetics traceable to a coupling between spin polarization and coherence in the relaxation process. As a consequence the NMRD curves do not directly reflect the spectral density function of the motional processes, but the effects of motion and spin coupling must be separated for a reliable evaluation. A theoretical approach is described allowing such an analysis.     

Determination of T1- and T2-relaxation times in the spleen of patients with splenomegaly

Twenty-nine patients with known splenomegaly and seven healthy volunteers were examined. The T1 and T2 relaxation times were read out from a region of interest centrally in the spleen. Even though different mean T1 and T2 relaxation times were found between the groups, the great scatter and the considerable overlap between the groups makes the contribution of relaxation time measurements to the differential diagnosis of splenomegaly of limited value.     

Detection of a systemic effect of malignancy in vivo by magnetic resonance imaging

In animals bearing tumors prolongation of spin lattice relaxation time (T1) has been detected in vitro in organs not directly affected by the malignancy. This has been termed the "Systemic Effect." In this study the possible existence of such an effect in the liver, muscle and fat of humans with lymphoma has been investigated. In vivo T1 measurements were made using a low field strength (0.08 Tesla) magnetic resonance imager. The mean liver T1 for 19 lymphoma patients with normal liver histology was 206 ms, compared with a mean of 191 ms for 61 volunteers (p less than 0.0001). Among these patients prolongation of liver T1 was related to the extent of disease elsewhere in the body. For 23 patients with Hodgkin's disease (HD) examined at the time of diagnosis, liver T1 was significantly correlated with other known markers of disease extent or activity (alkaline phosphatase level, erythrocyte sedimentation rate and the presence of systemic symptoms). No such correlations were observed among 25 patients with non-Hodgkin's lymphoma (NHL). Muscle and fat T1 was measured in 26 patients with lymphoma, 14 patients with acute leukemia and 88 volunteers. Seven of the patients with lymphoma and 2 of those with leukemia had muscle T1 values above the range observed for volunteers. Similarly, 3 patients with lymphoma and 1 with leukemia had prolonged fat T1. These findings indicate that a systemic effect of malignancy on T1 is detectable in a proportion of humans with lymphoma or leukemia.     

Prolonged T1 in patients with liver cirrhosis: an in vivo MRI study

Fifteen patients with liver cirrhosis and two control groups were examined. The first control group consisted of 7 healthy volunteers, and the second group of 17 patients with nonfocal liver diseases. The T1 and T2 relaxation times were calculated from signal intensities read out from a region of interest centrally located in the liver. T1 relaxation time was longer in the patients with liver cirrhosis than in the two reference groups. Ten patients had a liver biopsy taken prior to the MRI study. No correlation was found between histopathology and the measured relaxation times.     

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.     

Magnetic resonance imaging in patients with unstable angina: comparison with acute myocardial infarction and normals

The role of magnetic resonance imaging in characterizing normal, ischemic and infarcted segments of myocardium was examined in 8 patients with unstable angina, 11 patients with acute myocardial infarction, and 7 patients with stable angina. Eleven normal volunteers were imaged for comparison. Myocardial segments in short axis magnetic resonance images were classified as normal or abnormal on the basis of perfusion changes observed in thallium-201 images in 22 patients and according to the electrocariographic localization of infarction in 4 patients. T2 relaxation time was measured in 57 myocardial segments with abnormal perfusion (24 with reversible and 33 with irreversible perfusion changes) and in 25 normally perfused segments. T2 measurements in normally perfused segments of patients with acute myocardial infarction, unstable angina and stable angina were within normal range derived from T2 measurements in 48 myocardial segments of 11 normal volunteers (42 +/- 10 ms). T2 in abnormal myocardial segments of patients with stable angina also was not significantly different from normal. T2 of abnormal segments in patients with unstable angina (64 +/- 14 in reversibly ischemic and 67 +/- 21 in the irreversibly ischemic segments) was prolonged when compared to normal (p less than 0.0001) and was not significantly different from T2 in abnormal segments of patients with acute myocardial infarction (62 +/- 18 for reversibly and 66 +/- 11 for irreversibly ischemic segments). The data indicate that T2 prolongation is not specific for acute myocardial infarction and may be observed in abnormally perfused segments of patients with unstable angina.(ABSTRACT TRUNCATED AT 250 WORDS)     

Measurement of T1 of human arterial and venous blood at 7 T

Techniques for measuring cerebral perfusion require accurate longitudinal relaxation (T1) of blood, an MRI parameter that is field dependent. T1 of arterial and venous human blood was measured at 7 T using three different sources — pathology laboratory, blood bank and in vivo. The T1 of venous blood was measured from sealed samples from a pathology lab and in vivo. Samples from a blood bank were oxygenated and mixed to obtain different physiological concentrations of hematocrit and oxygenation. T1 relaxation times were estimated using a three-point fit to a simple inversion recovery equation. At 37 °C, the T1 of blood at arterial pO₂ was 2.29 ± 0.1 s and 2.07 ± 0.12 at venous pO₂. The in vivo T1 of venous blood, in three subjects, was slightly longer at 2.45 ± 0.11 s. T1 of arterial and venous blood at 7 T was measured and found to be significantly different. The T1 values were longer in vivo than in vitro. While the exact cause for the discrepancy is unknown, the additives in the blood samples, degradation during experiment, oxygenation differences, and the non-stagnant nature of blood in vivo could be potential contributors to the lower values of T1 in the venous samples.     

Determination of relaxation characteristics during preacute stage of lysophosphatidyl choline-induced demyelinating lesion in rat brain: an animal model of multiple sclerosis

Relaxation time measurements were carried out during the preacute stage of lesion progression in an animal model of demyelination created in the internal capsule (ic) area of the rat brain using lysophosphatidyl choline (LPC). T1 and T2 were determined both before and after 36 h of lesion creation. Histology carried out on the rats after MR measurements showed focal demyelinating lesion and surrounding edema with prominent infiltration of inflammatory cells. Both T1 and T2 were statistically higher for the lesion compared to that determined before lesion creation. Percentage increase in T2 was found to be higher by approximately 45% compared to before lesion creation while T1 showed about 25% increase. Increase in T1 and T2 may be attributed to the early acute inflammatory response due to LPC. The beginning of the inflammatory response following LPC injection may also be a contributing factor. The study demonstrates that the quantitative estimate of MR relaxation provides useful information on the pathological events occurring during the early phase of the progression of demyelination.     

Quantification of cerebral metabolites in glioma patients with proton MR spectroscopy using T2 relaxation time correction

This study was aimed to investigate the significance of absolute concentration of metabolites in glioma patients using proton MR spectroscopy (MRS) with T2 relaxation time correction using three different echo times. The absolute concentrations of metabolites in 7 normal subjects and in 23 gliomas (10 low-grade, 13 high-grade) were obtained by proton MRS using a tissue water signal as an internal standard. The signal intensities of metabolites and tissue water were corrected by T2 relaxation time. In low-grade glioma, the T2 relaxation time of NAA was shorter, and T2 relaxation time of water was prolonged as compared to normal subjects (p < 0.001). In high-grade glioma, the T2 relaxation time of NAA (p < 0.001) and T2 relaxation time of Cr (p < 0.01) were shorter, and T2 relaxation time of water (p < 0.001) was prolonged as compared to normal subjects. Moreover, high-grade gliomas revealed a shorter T2 relaxation time of Cr than low-grade gliomas (p < 0.05). In glioma, NAA and Cr concentration were decreased, and Cho were increased as compared to normal subjects. Moreover, high-grade glioma revealed a significant lower Cr (p < 0.001) and Cho (p < 0.01) concentration compared to low-grade gliomas. Low Cr concentration is the most reliable indicator of malignancy in glioma. Cho concentration did not correlate with malignancy in gliomas.     

Relaxo-volumetric multispectral quantitative magnetic resonance imaging of the brain over the human lifespan: global and regional aging patterns

The objective of this study was to determine the T1, T2 and secular-T2 relaxo-volumetric brain aging patterns using multispectral quantitative magnetic resonance imaging, both globally and regionally, and covering an age range approaching the full human lifespan. Fifty-one subjects (28 males, 23 females; age range: 0.5–87 years) were studied consisting of 18 healthy volunteers and 33 patients. Patients were selected after carefully reviewing their radiology reports to have either normal-by-MRI findings (25 patient subjects) or small focal pathology less than 6 mm in size (eight patient subjects). All subjects were MR imaged at 1.5 T with the mixed turbo spin echo pulse sequence. The soft tissues inside the cranial vault, termed intracranial matter (ICM), were segmented using a dual-clustering segmentation algorithm. ICM segments were further divided into six subsegments: bilateral anterior cerebral, posterior cerebral and cerebellar subsegments. T1, T2 and secular-T2 relaxation time histograms of all segments were generated and modeled with Gaussian functions. For each segment, the volumes of white matter, gray matter and cerebrospinal fluid were calculated from the T1 histograms. The age-related tendencies of three quantitative MRI parameters (T1, T2 and secular-T2) and the fractional tissue volumes showed four distinct periods of life, specifically a maturation period (0–2 years), a development period (2–20 years), an adulthood period (20–60 years) and a senescence period (60 years and older). For all ages, the anterior cerebral subsegment exhibited consistently longer gray matter T1s and shorter white matter T1s than the posterior cerebral and cerebellar subsegments. Volumetric age-related changes of the cerebellar subsegment were more gradual than in the cerebral subsegments. This study shows that relaxometric and volumetric age-related changes are synchronized and define the same four periods of brain evolution both globally and regionally.