Three-dimensional magnetic resonance spectroscopic imaging of histologically confirmed brain tumors

The goal of this study was to determine whether presurgical metabolite levels measured by 3D MR Spectroscopic Imaging (MRSI) can accurately detect viable cancer within human brain tumor masses. A total of 31 patients (33 exams, 39 pathology correlations) with brain tumors were studied prior to surgical biopsy and/or resection. The 3D MRSI was obtained with a spatial resolution of 0.2 to 1 cc throughout the majority of the mass and adjacent brain tissue using PRESS-CSI localization. Levels of choline, creatine and NAA were estimated from the locations of the resected tissue and normalized to normal appearing brain tissue. The data were correlated with subsequent histologic analysis of the biopsy tissue samples. Although there were large variations in the metabolite ratios, all regions of confirmed cancer demonstrated significant choline levels and a mean choline/NAA ratio of 5.84 + 2.58 with the lowest value being 1.3. This lowest value is greater than 4 standard deviations above the mean (0.52 +/- 0.13) found in 8 normal volunteers. The choline signal intensities in confirmed cancers were significantly elevated compared to normal appearing brain tissue with a mean ratio of 1.71 +/- 0.69. Spectra with no significant metabolite levels were observed in the non-enhancing necrotic core of the tumor masses. The results of this study indicate that 3D MRSI of brain tumors can detect abnormal metabolite levels in regions of viable cancer and grades and can differentiate cancer from necrosis and/or normal brain tissue.     

Gd HP-DO3A--experimental evaluation in brain and renal MR

GD HP-DO3A, a neutral (nonionic) IV MR contrast agent presently in clinical trials, was evaluated with respect to imaging characteristics in rats. Following administration of 0.25 mmol/kg I.V., 58 +/- 19%, i.e. (n = 6) enhancement was noted in a brain gliosarcoma model. Meningeal spread of neoplasia could be identified due to its enhancement (69 +/- 26%) in nine animals. The time course of renal enhancement was quantitated at two dosages, 0.05 (n = 4) and 0.25 mmol/kg (n = 8). At the higher dose, enhancement of both cortex and medulla plateaued between 9 and 23 min postinjection. At the lower dose, enhancement of renal medulla was maximum at 2 min postinjection. These enhancement characteristics (both brain and kidney), at equivalent contrast dosages, are comparable to that previously published for Gd-DTPA. However, Gd HP-DO3A has the potential to be utilized clinically at higher doses than Gd-DTPA, with no reported adverse effects in initial trials employing up to 0.3 mmol/kg.     

Measurement of the extracellular volume of human melanoma xenografts by contrast enhanced magnetic resonance imaging

The magnitude of the extracellular volume fraction (ECV) of tumors is of importance for the transport of macromolecular therapeutic agents from the vessel wall to the tumor cells. The aim of this study was to develop a method for measurement of tumor ECV by contrast enhanced MRI. Tumors of two human amelanotic melanoma xenograft lines (A-07 and R-18) grown intradermally in Balb/c nu/nu mice were used as model system, and muscle tissue was used as control. The renal arteries of the mice were ligated prior to i.v. administration of Gd-DTPA, and an MRI protocol for calculating Gd-DTPA concentration in tissue was followed. ECV was calculated from the Gd-DTPA concentrations in the tissue and in a plasma sample. In muscle tissue, the concentration reached a constant level after 1 min and the ECV was calculated to be 0.12 (+/- 0.01), consistent with values reported in the literature. Individual tumors showed large differences in the uptake of Gd-DTPA. The Gd-DTPA concentration in the tissue at 40 min after the Gd-DTPA administration was used to calculate tumor ECV. The ECV was found to differ significantly among regions of individual tumors and among individual tumors. The ECV ranged from 0.075 to 0.33 for A-07 tumors and from 0.016 to 0.097 for R-18 tumors. The intra- and intertumor heterogeneity in ECV was confirmed by histologic findings, showing that contrast enhanced MRI is suitable for non-invasive studies of the ECV in experimental tumors without necrosis.     

Phosphorus-31 MR spectroscopic imaging (MRSI) of normal and pathological human brains.

The goals of this study were to evaluate 31P MR spectroscopic imaging (MRSI) for clinical studies and to survey potentially significant spatial variations of 31P metabolite signals in normal and pathological human brains. In normal brains, chemical shifts and metabolite ratios corrected for saturation were similar to previous studies using single-volume localization techniques (n = 10; pH = 7.01 +/- 0.02; PCr/Pi = 2.0 +/- 0.4; PCr/ATP = 1.4 +/- 0.2; ATP/Pi = 1.6 +/- 0.2; PCr/PDE = 0.52 +/- 0.06; PCr/PME = 1.3 +/- 0.2; [Mg2+]free = 0.26 +/- 0.02 mM.) In 17 pathological case studies, ratios of 31P metabolite signals between the pathological regions and normal-appearing (usually homologous contralateral) regions were obtained. First, in subacute and chronic infarctions (n = 9) decreased Pi (65 +/- 12%), PCr (38 +/- 6%), ATP (55 +/- 6%), PDE (47 +/- 9%), and total 31P metabolite signals (50 +/- 8%) were observed. Second, regions of decreased total 31P metabolite signals were observed in normal pressure hydrocephalus (NPH, n = 2), glioblastoma (n = 2), temporal lobe epilepsy (n = 2), and transient ischemic attacks (TIAs, n = 2). Third, alkalosis was detected in the NPH periventricular tissue, glioblastoma, epilepsy ipsilateral ictal foci, and chronic infarction regions; acidosis was detected in subacute infarction regions. Fourth, in TIAs with no MRI-detected infarction, regions consistent with transient neurological deficits were detected with decreased Pi, ATP, and total 31P metabolite signals. These results demonstrate an advantage of 31P MRSI over single-volume 31P MRS techniques in that metabolite information is derived simultaneously from multiple regions of brain, including those outside the primary pathological region of interest. These preliminary findings also suggest that abnormal metabolite distributions may be detected in regions that appear normal on MR images.     

Anisotropy of the backscatter coefficient of formalin-fixed ovine myocardium

The objective of this study was to measure the backscatter coefficient of formalin-fixed myocardial tissue as a function of angle of insonification relative to the myocardial fiber direction. Backscatter measurements were performed on eight cylindrical formalin-fixed lamb myocardial specimens and compensated for attenuation and diffraction effects to determine the backscatter coefficient. The backscatter coefficient at 5 MHz was found to be maximum for insonification perpendicular to the predominant myofiber orientation and minimum for parallel insonification, with values of (17+/-14) and (1.2+/-0.7) x 10(-4) cm(-1) sr(-1) (mean+/-standard deviation), respectively.     

Improved T(1)-weighted dynamic contrast-enhanced MRI to probe microvascularity and heterogeneity of human glioma

Dynamic contrast-enhanced (DCE) T(1)-weighted magnetic resonance imaging (MRI) is a powerful tool capable of providing quantitative assessment of contrast uptake and characterization of microvascular structure in human gliomas. The kinetics of the bolus injection doped with increasing concentrations of gadopentate dimeglumine (Gd-DTPA) depends on tissue as well as pulse sequence parameters. A simple method is described that overcomes the limitation of relative signal increase measurement and may lead to improved accuracy in quantification of perfusion indices of glioma. Based on an analysis of the contrast behavior of spoiled gradient-recalled echo sequence; a parameter K with arbitrary unit 5.0 is introduced, which provides a better approximation to the differential T(1) relaxation rate. DCE-MRI measurements of relative cerebral blood volume (rCBV) and cerebral blood flow (rCBF) were calculated in 25 patients with brain tumors (15=high-grade glioma, 10=low-grade glioma). The mean rCBV was 6.46 +/- 2.45 in high-grade glioma and 2.89 +/- 1.47 in the low-grade glioma. The rCBF was 3.94 +/- 1.47 in high-grade glioma while 2.25 +/- 0.87 in low-grade glioma. A significant difference in rCBF and rCBV was found between high- and low-grade gliomas. This simple and robust technique reveals the complexity of tumor vasculature and heterogeneity that may aid in therapeutic management especially in nonenhancing high-grade gliomas. We conclude that the precontrast medium steady-state residue parameter K may be useful in improved quantification of perfusion indices in human glioma using T(1)-weighted DCE-MRI.     

MR imaging of the arthritic rabbit knee joint using albumin-(Gd-DTPA)30 with correlation to histopathology

The purpose of this study was to demonstrate a technique, in a pilot study, for measuring abnormal capillary permeability in synovial tissue of rabbit arthritic knees using dynamic MRI with a gadolinium-based blood pool agent. Arthritis, simulating rheumatoid arthritis, was induced in knees of 8 rabbits by intra-articular injection of carrageenan (n = 4) or ovalbumin (n = 4). Sequential fat presaturated T1-weighted Spoiled Grass images were obtained before and up to 30 min after intravenous administration of albumin-(Gd-DTPA)30. Estimates of synovial tissue plasma-volume (PV), fractional-leak-rate (FLR), and permeability-surface-area-product (PS) were computed. Histologic correlation was obtained in the corresponding regions. Dynamic MRI showed extravasation of albumin-(Gd-DTPA)30 into hypertrophic synovium in six of the eight arthritic knees. Histologic examination of these six knees showed markedly inflamed synovium. The two knees that did not show abnormal vascular permeability contained non-hypertrophic synovium. None of the rabbits showed abnormal permeability in muscle. MRI derived microvascular characteristics (PV, FLR and PS) correlated positively (r2 = 0.51, 0.97 and 0.86) with the histology. Factors involving the structural and functional microvascular characteristics of synovial tissue can be estimated non-invasively using albumin-(Gd-DTPA)30. This technique may be useful for monitoring disease progression and treatment response in rheumatoid arthritis.     

Diffusion of paramagnetically labeled proteins in cartilage: enhancement of the 1-D NMR imaging technique

Quantifying the diffusive transport of large molecules in avascular cartilage tissue is important both for planning potential pharamacological treatments and for gaining insight into the molecular-scale structure of cartilage. In this work, the diffusion coefficients of gadolinium-DTPA and Gd-labeled versions of four proteins-lysozyme, trypsinogen, ovalbumin, and bovine serum albumin (BSA) with molecular weights of 14,300, 24,000, 45,000, and 67,000, respectively-have been measured in healthy and degraded calf cartilage. The experimental technique relies on the effect of the paramagnetic on the relaxation properties of the surrounding water, combined with the time course of a 1-dimensional spatial profile of the water signal in the cartilage sample. The enhanced technique presented here does not require a prior measurement of the relaxivity of the paramagnetic compound in the sample of interest. The data are expressed as the ratio of the diffusion coefficient of a compound in cartilage to its diffusion coefficient in water. For healthy cartilage, this ratio was 0.34 +/- 0.07 for Gd-DTPA, the smallest compound, and fell to 0.3 +/- 0.1 for Gd-lysozyme, 0.08 +/- 0.04 for Gd-trypsinogen, and 0.07 +/- 0.04 for Gd-ovalbumin. Gd-BSA did not appear to enter healthy cartilage tissue beyond a surface layer. After the cartilage had been degraded by 24-h trypsinization, these ratios were 0.60 +/- 0.03 for Gd-DTPA, 0.40 +/- 0.08 for Gd-lysozyme, 0.42 +/- 0.09 for Gd-trypsinogen, 0.16 +/- 0.14 for Gd-ovalbumin, and 0.11 +/- 0.05 for Gd-BSA. Thus, degradation of the cartilage led to increases in the diffusion coefficient of up to fivefold for the Gd-labeled proteins. These basic transport parameters yield insights on the nature of pore sizes and chemical-matrix interactions in the cartilage tissue and may prove diagnostically useful for identifying the degree and nature of damage to cartilage.     

Excimer laser spectroscopy: influence of tissue ablation on vessel wall fluorescence

Limited steerability and injury to the normal vessel wall are major drawbacks of laser coronary angioplasty. To overcome these limitations a new generation of laser systems has been developed which allows not only to eliminate the atherosclerotic plaque but to guide the laser beam by analyzing the laser induced tissue fluorescence (= spectroscopy) for the treatment of the atherosclerotic vessel. An excimer laser (MAX 10 LP, 308 nm, Technolas, Munich, Germany) was used with an emitting (phi 1070 microns) and a detecting (phi 130 microns) optical fiber to induce tissue fluorescence which was analyzed quantitatively by a computerized system. Specimens from the descending (thoracic) aorta were obtained from 24 patients (mean age 68.1 years, range 44-92). Tissue fluorescence was induced with ablating (26-30 mJ/mm2) and nonablating (3 mJ/cm2) laser activations. The emitted fluorescence (range 380-575 nm) was normalized to a wavelength of 380 nm; as a measure of tissue fluorescence the intensity ratio at 500 nm divided by 400 nm was calculated in normal (n = 78), mildly atherosclerotic (n = 40), and severely atherosclerotic (n = 48) tissue samples. Repeated laser activations were carried out and tissue fluorescence was checked until the fluorescence spectrum was normalized. All tissue samples were analyzed histologically by a semiquantitative score. Normal tissue samples showed the highest intensity ratios (5.9 +/- 3.4), whereas mildly (2.9 +/- 1.3) and severely atherosclerotic (2.1 +/- 1.0) samples elicited a significantly reduced fluorescence. Repeated tissue ablations were associated with a normalization of fluorescence intensity ratios in the mildly (7.0) as well as in the severely diseased (4.9) vessels. A curvilinear relationship between intensity ratio and the semiquantitative score was observed (r = 0.66) as well as between intensity ratio and intimal wall thickness (r = 0.62). No gender related differences were found but there was an inverse relationship between fluorescence intensity ratio and age (r = 0.56) as well as between intimal thickness and age (r = 0.41). Excimer laser spectroscopy allows reliable detection of atherosclerotic vessel alterations. Fluorescence intensity ratio is inversely proportional to the intimal wall thickness and the severity of the histologic alterations. There is an age dependency of fluorescence intensity ratio which can be explained by an increase in intimal wall thickness. Successful tissue ablation can be obtained by laser angioplasty and allows determination of the optimal point where complete tissue ablation is achieved by laser activation. Thus, excimer laser spectroscopy is an effective method for selective tissue ablation by laser angioplasty.     

Prostatic tissue ablation by transrectal high intensity focused ultrasound: histological impact and clinical application

In a phase-I clinical trial the morphologic impact and safety of high-intensity focused ultrasound (HIFU) administered transrectally for tissue ablation in human prostates (n = 54) was evaluated. Location and size of the tissue lesions correlated well with the predefined target area and revealed sharply delineated coagulative necrosis in all cases. Intervening tissues, such as the rectal wall and posterior prostate capsule were invariably intact. In a subsequent phase-II clinical trial safety and efficacy of transrectal HIFU as a novel minimally invasive treatment modality for patients with symptomatic benign prostatic hyperplasia (BPH; n = 102) was determined. The maximum urinary flow rate (Qmax, ml/s) increased from 9.1+/-4.0 to 12.9+/-6.1 (3 months, n=86), 12.7+/-5.1 (6 months, n=78) and 13.3+/-6.1 (12 months, n=56). In the same time period the post void residual volume (ml) decreased from 131+/-115 to 46+/-45, 57+/-46 and 48+/-36 and the AUA symptom score decreased from 24.5+/-4.7 to 13.3+/-4.4, 13.4+/-4.7 and 10.8+/-2.5. A subset of patients (n=30) underwent multichannel pressure flow studies, which demonstrated that transrectal HIFU reduces bladder outflow obstruction. These data demonstrate that transrectal HIFU is capable of inducing coagulative necrosis in the human prostate via a transrectal approach while preserving intervening and adjacent tissue. A 48% improvement of uroflow and a 53% decrease of urinary symptoms 1 year after treatment prove that transrectal HIFU is an effective and safe minimally invasive treatment option for BPH.     

Two-exponential analysis of spin-spin proton relaxation times in MR imaging using surface coils

Proton relaxation time measurements were performed on a standard whole body MR imager operating at 1.5 T using a conventional surface coil of the manufacturer. A combined CP/CPMG multiecho, multislice sequence was used for the T1 and T2 relaxation time measurements. Two repetition times of 2000 ms (30 echoes) and 600 ms (2 echoes) with 180 degrees-pulse intervals of 2 tau = 22 ms were interleaved in this sequence. A two-exponential T2 analysis of each pixel of the spin-echo images was computed in a case of an acoustic neurinoma. The two-exponential images show a "short" component (T2S) due to white and gray matter and a "long" component (T2S) due to the cerebrospinal fluid. In the fatty tissue two components with T2S = 35 +/- 3 ms and T2L = 164 +/- 7 ms were measured. Comparing with Gd-DTPA imaging the relaxation time images show a clear differentiation of vital tumor tissue and cerebrospinal fluid.     

Assessment of T1 time course changes and tissue-blood ratios after Gd-DTPA administration in brain tumors

Sequential T1 changes in brain tumor tissue after Gd-DTPA administration were investigated in 10 patients, including 4 meningiomas, 2 gliomas, 3 metastatic cerebral tumors and 1 brain abscess. T1 values were measured serially for 60 minutes following Gd-DTPA injection using a magnetic focusing technique. In vitro T1 of the whole blood samples was also comparatively examined. Time processes in the tissue-blood ratio (TBR) were calculated from two-point relaxation rates at 5 and 30 minutes. The obtained ratios of TBR were ranged from 1.0 to 3.0, probably depending on histological types of brain tumor (the value of 1.0 to 1.5 for meningioma and 1.5 to 3.0 for glioma and metastatic tumor). No significant changes in the T1 value were observed in the examined normal tissue and peritumoral edema. These results indicate that Gd-DTPA plays an important role not only as an image enhancer for tumor tissue but also as an indicator for estimating the blood-brain barrier function.     

Differentiation of recurrent brain tumor versus radiation injury using diffusion tensor imaging in patients with new contrast-enhancing lesions

BACKGROUND AND PURPOSE: The purpose of this study was to assess the use of diffusion tensor imaging (DTI) in the evaluation of new contrast-enhancing lesions and perilesional edema in patients previously treated for brain neoplasm in the differentiation of recurrent neoplasm from treatment-related injury. METHODS: Twenty-eight patients with new contrast-enhancing lesions and perilesional edema at the site of previously treated brain neoplasms were retrospectively reviewed. Nine directional echoplanar DTIs with b=1000 s/mm(2) were obtained using a single-shot spin-echo echoplanar imaging. Standardized regions of interest were manually drawn in several regions. Mean apparent diffusion coefficient (ADC), fractional anisotropy (FA) and eigenvalue indices (lambda( parallel) and lambda( perpendicular)) and their ratios relative to the contralateral side were compared in patients with recurrent neoplasm versus patients with radiation injury, as established by histological examination or by clinical course, including long-term imaging studies and magnetic resonance spectroscopy. RESULTS: The ADC values in the contrast-enhancing lesions were significantly higher (P=.01) for the recurrence group (range=1.01 x 10(-3) to 1.66 x 10(-3) mm(2)/s; mean+/-S.D.=1.27+/-0.15) than for the nonrecurrence group (range=0.9 x 10(-3) to 1.31 x 10(-3) mm(2)/s; mean+/-S.D.=1.12+/-0.14). The ADC ratios in the white matter tracts in perilesional edema trended higher (P=.09) in treatment-related injury than in recurrent neoplasm (mean+/-S.D.=1.85+/-0.30 vs. 1.60+/-0.27, respectively). FA ratios were significantly higher in normal-appearing white matter (NAWM) tracts adjacent to the edema in the nonrecurrence group (mean+/-S.D.=0.89+/-0.15) than in those in the recurrence group (mean+/-S.D.=0.74+/-0.14; P=.03). Both eigenvalue indices lambda( parallel) and lambda( perpendicular) were significantly higher in contrast-enhancing lesions in the recurrence group than in those in the nonrecurrence group (P=.02). As well, both eigenvalue indices lambda( parallel) and lambda( perpendicular) were significantly higher in perilesional edema than in normal white matter (P<.01 and P<.001, respectively) in both groups. CONCLUSION: The assessment of diffusion properties, especially ADC values and ADC ratios, in contrast-enhancing lesions, perilesional edema and NAWM adjacent to the edema in the follow-up of new contrast-enhancing lesions at the site of previously treated brain neoplasms may add to the information obtained by other imaging techniques in the differentiation of radiation injury from tumor recurrence.     

Elevations of diffusion anisotropy are associated with hyper-acute stroke: a serial imaging study

Diffusion tensor imaging (DTI) studies of human ischemic stroke within 24 h of symptom onset have reported variable findings of changes in diffusion anisotropy. Serial DTI within 24 h may clarify these heterogeneous results. We characterized longitudinal changes of diffusion anisotropy by analyzing discrete ischemic white matter (WM) and gray matter (GM) regions during the hyperacute (2.5-7 h) and acute (21.5-29 h) scanning phases of ischemic stroke onset in 13 patients. Mean diffusivity (MD), fractional anisotropy (FA) and T2-weighted signal intensity were measured for deep and subcortical WM and deep and cortical GM areas in lesions outlined by a > or =30% decrease in MD. Average reductions of approximately 40% in relative (r) MD were observed in all four brain regions during both the hyperacute and acute phases post stroke. Overall, 9 of 13 patients within 7 h post symptom onset showed elevated FA in at least one of the four tissues, and within the same cohort, 11 of 13 patients showed reduced FA in at least one of the ischemic WM and GM regions at 21.5-29 h after stroke. The fractional anisotropy in the lesion relative to the contralateral side (rFA, mean+/-S.D.) was significantly elevated in some patients in the deep WM (1.10+/-0.11, n=4), subcortical WM (1.13+/-0.14, n=4), deep GM (1.07+/-0.06, n=1) and cortical GM (1.22+/-0.13, n=5) hyperacutely (< or =7 h); however, reductions of rFA at approximately 24 h post stroke were more consistent (rFA= 0.85+/-0.12).     

Characterizing blood volume fraction (BVF) in a VX2 tumor

OBJECTIVES: Neovascular proliferation of a tumor's blood supply is an important precursor of malignant growth. Evaluation of blood volume may provide useful information for the characterization, prognosis and response of tumors to therapy. The purpose of this study was to determine and compare the blood volume of tumor tissue measured noninvasively by MRI and microbubble contrast ultrasound imaging. MATERIALS AND METHODS: Twenty-two rabbits injected with VX2 tumors were studied. The blood volume fraction in tumor and muscle tissue was obtained from MRI T(1)-weighted images using a blood-pool agent, Clariscan, and by ultrasound using Definity and pulse inversion imaging. RESULTS AND CONCLUSIONS: Similar results were obtained from MRI and ultrasound. Estimation of the blood volume in tissue in the rim of a VX2 tumor 1.5 to 5.0 cm in diameter relative to that in the surrounding muscle was (mean+/-S.D.) 3.31+/-1.43 by MRI and 2.99+/-1.83 by ultrasound. The blood volume in the tissue relative to the total tissue volume (relative blood volume fraction) measured by MRI was 13+/-4.1% in tumor versus 4+/-1.4% in muscle (P<.01). Our data also suggested that, compared to the distribution volume of an extracellular contrast agent, Gd-DTPA, Clariscan as an intravascular agent demonstrated high-quality depictions of vascular structure of the tumor.     

The zonal architecture of human articular cartilage described by T2 relaxation time in the presence of Gd-DTPA2-

The depth-wise variation of T(2) relaxation time is known to reflect the collagen network architecture in cartilage, while the delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) technique is sensitive to tissue proteoglycan (PG) concentration. As the cartilage PG content varies along the tissue depth, the depth-dependent accumulation of the contrast agent may affect the inherent T(2) of cartilage in a nonconstant manner. Therefore, T(2) and dGEMRIC are typically measured in separate MRI sessions. In the present in vitro MRI study at 9.4 T, depth-wise T(2) profiles and collagenous zone thicknesses as determined from T(2) maps in the absence and presence of Gd-DTPA(2-) (T(2) and T(2Gd), respectively) were compared in samples of intact human articular cartilage (n=65). These T(2) measures were further correlated with birefringence (BF) of polarized light microscopy (PLM) to quantify the ability of MRI to predict the properties of the collagen fibril network. The reproducibility of the T(2) measurement in the current setup was also studied. Typical tri-laminar collagen network architecture was observed both with and without Gd-DTPA(2-). The inverse of BF (1/BF) correlated significantly with both T(2) and T(2Gd) (r=0.91, slope=0.56 and r=0.90, slope=0.63), respectively. The statistically significant linear correlations between zone thicknesses as determined from T(2) and T(2Gd) were r=0.55 (slope=0.49), r=0.74 (slope=0.71) and r=0.95 (slope=0.94) for superficial, middle and deep tissue zones, respectively. Reproducibility of the T(2) measurement was worst for superficial cartilage. Consistent with PLM, T(2) and T(2Gd) measurements reveal highly similar depth-dependent information on collagen network in intact human cartilage. Thus, dGEMRIC and T(2) measurements in one MRI session are feasible for intact articular cartilage in vitro.     

3D spin-lock imaging of human gliomas

We investigated whether the simultaneous use of paramagnetic contrast medium and 3D on-resonance spin lock (SL) imaging could improve the contrast of enhancing brain tumors at 0.1 T. A phantom containing serial concentrations of gadopentetate dimeglumine (Gd-DTPA) in cross-linked bovine serum albumin (BSA) was imaged. Eleven patients with histologically verified glioma were also studied. T₁-weighted 3D gradient echo images with and without SL pulse were acquired before and after a Gd-DTPA injection. SL effect, contrast, and contrast-to-noise ratio (CNR) were calculated for each patient. In the glioma patients, the SL effect was significantly smaller in the tumor than in the white and gray matter both before (p = 0.001, p = 0.025, respectively), and after contrast medium injection (p < 0.001, p < 0.001, respectively). On post-contrast images, SL imaging significantly improved tumor contrast (p = 0.001) whereas tumor CNR decreased slightly (p = 0.024). The combined use of SL imaging and paramagnetic Gd-DTPA contrast agent offers a modality for improving tumor contrast in magnetic resonance imaging (MRI) of enhancing brain tumors. 3D gradient echo SL imaging has also shown potential to increase tissue characterization properties of MR imaging of human gliomas.     

The use of a micro-bubble agent to enhance rabbit liver destruction using high intensity focused ultrasound

Liver tissues in New Zealand rabbits were ablated using high intensity focused ultrasound (HIFU, 14300 W/cm(2), 1.0 MHz). The animals were intravenously administered 0.2 ml of micro-bubble agent in the experimental (n=20) group and an isovolumetric normal saline solution in the control (n=27) group before HIFU treatment which was performed as a linear scan. In both groups, the preselected tissue volumes were destroyed without harming the overlying tissues. Necrosis rate (NR, cm(3)/s) was used to reflect the ablation efficiency, which was the tissue volume of occurring coagulative necrosis per 1s HIFU exposure. NR was improved in the experimental group (0.0570+/-0.0433 vs 0.0120+/-0.0122, P=0.0002). Pathological studies confirmed that there were no residual intact targets within the exposed volume. These findings suggested that the introduction of the micro-bubble agent enhanced HIFU liver destruction.     

Biodistribution of GdCl3 and Gd-DTPA and their influence on proton magnetic relaxation in rat tissues

The biodistribution and relative molar effectiveness of the ionic (GdCl3) and chelated (Gd-DTPA) forms of gadolinium (Gd) to enhance proton relaxation rates in rat kidney, liver and spleen were evaluated. Rats were given intravenous injections of either GdCl3 (100 mumol/kg) or Gd-DTPA (178 mumol/kg). Gd-DTPA was primarily contained in the vascular compartment and was quickly accumulated in the kidney after injection with a relaxivity of 4.3 sec-1 (mumol/g kidney)-1. It was eliminated quickly from the body with only 2% of the injected dose remaining after 120 min. After GdCl3 injection, Gd was found primarily in liver and spleen. It accumulated continuously reaching 72% of the injected does in these two tissues after 120 min. Despite this continuous increase in tissue Gd concentration, the relaxation rates showed saturation in liver and spleen. The results suggest that after GdCl3 was injected it distributed either in a protein bound form that was effective at causing relaxation or in a colloid form that was not effective. The biodistribution of GdCl3 was such that it was determined by the phagocytic action of the recticuloendothelial system on a colloid. The biodistribution and tissue relaxivity of Gd-DTPA suggest it will be a useful vascular MRI contrast agent. However, the usefulness of GdCl3 as an MRI contrast agent is limited not only by its acute toxicity but also by its saturable effect on tissue relaxation rates. Consequently, GdCl3 has only a modest influence on tissue relaxivity.     

Evaluation of CH3-DTPA-Gd (NMS60) as a new MR contrast agent: early phase II study in brain tumors and dual dynamic contrast-enhanced imaging

PURPOSE: A newly developed contrast material, CH3-DTPA-Gd (NMS60), a trimer containing 3 Gd(3+) atoms per molecule, has been shown to offer greater enhancement and longer vascular retention than gadopentetate dimeglumine (Gd-DTPA) in animals. We report on our early phase II study on NMS60 in brain tumor patients together with supplementary investigations. METHODS AND MATERIALS: The longitudinal relaxation rate (R(1)=1/T(1)) and the transverse relaxation rate (R(2)*=1/T(2)*) of NMS60 and Gd-DTPA were determined at 20 degrees C in water at 1.5 T. An NMS60 dose of 0.1 or 0.2 mmol (Gd)/kg was randomly assigned and administered to 10 patients (five women, five men; mean age: 49 years) with brain tumors. Safety and contrast-enhancing ability of NMS60 were evaluated. Dual dynamic contrast-enhanced T(1) and R(2)* studies (DUCE imaging) were also carried out in two patients. RESULTS: Regarding the relaxivity per Gd, R(1) and R(2)* of NMS60 were 9.5 and 11.0 (mmol/L x s)(-1), respectively, compared to 4.8 and 7.2 (mmol/L x s)(-1) for Gd-DTPA. Although a transient slight increase of alanine aminotransferase was observed in one case, no other adverse reactions were observed after administration of NMS60. Contrast enhancement by NMS60 was excellent at both concentrations, and when tumor detectability was assessed with a five-point scale, the diagnostic usefulness was 4 or higher in all cases. In DUCE imaging, NMS60 appeared to show high signal intensity, when compared with the data obtained separately for Gd-DTPA. CONCLUSION: NMS60 had a high contrasting effect and little toxicity, and is expected to be clinically useful.