Age-related changes in proton T1 values of normal human brain

To determine whether there were age-related changes In the brain tissue of 55 healthy adult volunteers (29 men, 26 women; 18-72 years old) without known brain abnormalities, a standard inversion-recovery technique was optimized for precise and accurate T1 measurement within the constraints of a 15-minute examination. Measurements of water proton T1 were obtained in eight brain regions. T1 increased with age in the genu (P < 0.001) (analysis of variance), frontal white matter (P < 0.05), occipital white matter (P < 0.05), putamen (P < 0.001), and thalamus (P << 0.001). A significant decrease in T1 with age was found in cortical gray matter (P < 0.05). Thus, age-related changes in T1 are present in a healthy population, even if extremes of age are excluded, suggesting that T1 values generally increase with age. However, increases in T1 were also observed in the genu, putamen, and thalamus of a substantial fraction of volunteers less than 35 years old. Aging healthy persons can show subtle, nonsymp- tomatic brain changes, suggesting that brain aging is associated with occult processes that can begin at a relatively early age.     

A novel fast T1-mapping method

The authors present a novel fast T1-mapping technique that allows a T1 map to be reconstructed from data acquired in less than 3 seconds. Data were acquired by using two modified TurboFLASH (fast low-angle shot) sequences and were processed with a combination of one-dimensional Fourier transforms and a parameter-fitting routine, instead of a standard two-dimensional Fourier transform. Apparent T1 (T1*) maps were obtained, from which T1 maps were calculated. Comparisons of T1 values obtained in phantoms and the human brain by using this technique with those obtained with multipoint inversion-recovery T1 mapping showed that the new method yielded accurate T1 values. Optimization of the method will further improve speed and accuracy. The general approach of this T1-mapping technique is believed to be also applicable to other problems, such as T2 and T2* mapping.     

Metabolite concentrations in the developing brain estimated with proton MR spectroscopy

The purpose of the present study was to estimate absolute concentrations and relaxation time constants of metabolites that were detectable with proton magnetic resonance (MR) spectroscopy in the healthy preterm, term, and infant brain. Five MR spectra were recorded for each infant by using STEAM (stimulated-echo acquisition mode) sequences with different TEs and TRs. Water was used as an internal standard. The T1 of choline-containing compounds (Cho) and the T1 of phosphocreatine plus creatine (PCr+Cr) decreased. The T2 of the N-acetyl-L-aspartate (NAA) resonance increased, probably because of a relatively larger signal overlap with glutamate in the most immature brains. The concentration of NAA almost doubled, whereas the Cho concentration showed only a nonsignificant tendency to decrease; therefore, the well-known increase in the ratio of NAA to Cho appears to be due mostly to an increase in NAA concentration. The concentration of PCr+Cr increased rapidly and reached adolescent values at approximately 4 months of age.     

Interventricular differences in myocardial T2 measurements: experimental and clinical studies.

The goal of this study was to determine the accuracy, the reproducibility, and some of the tissue determinants of image-based myocardial T2 measurements. Image-based T2 calculations for the free walls of the right ventricle (RV) and left ventricle (LV), in vitro T2 determination (at 0.47 T), and water, fat, and collagen content analyses were performed in ex vivo hog hearts. T2 values of the RV and LV free walls were also determined from spin-echo images of 14 healthy human subjects. Preliminary reproducibility studies were performed with 10 sets of images acquired from a single subject. For both in vitro and image-based T2 values of hog hearts, RV T2 was significantly longer than LV T2. Water content was the only tissue factor to significantly correlate with in vitro and image-based T2 values. For the 14 human subjects studied, image-based T2 values calculated from the first- and third-echo images demonstrated a significant difference between LV and RV. The difference was not significant when the first- and second-echo images were used. Image-based T2 measurements of a single subject showed a coefficient of variation of 6.8% for the LV and 9.1% for the RV. The authors conclude that image-based T2 measurements of normal myocardium can be made with sufficient precision to identify differences of the magnitude of those found between RV and LV T2 values. Image-based T2 values of myocardium may provide useful data to aid in patient treatment.     

MR evaluation of cervical cancer in hysterectomy specimens: Correlation of quantitative T2 measurement and histology

Specimens from modified radical hysterectomies performed for invasive carcinoma of the cervix were analyzed with quantitative T2 magnetic resonance (MR) imaging and histologic study to determine to what degree there was a correlation between the findings of the two modalities. The mean T2 of cervical stroma was 48 msec, while the outer zone of the cervix had a mean T2 of 62 msec and the central canal region typically had T2 values of 115 msec ± 20 (standard deviation). A total of nine cervical cancers were analyzed, and their mean T2 value was 79 msec. Separation between cervical stroma and tumor was good, with stromal T2 values ranging from 30 to 66 msec, while tumor T2s ranged from 60 to 97 msec. Statistical analysis indicated that these data were associated with a sensitivity of 89% and a specificity of 95%, with 95% confidence intervals of [50%,99.4%] and [74%,99.7%], respectively, for separating tumor from stroma on the basis of T2 value. Quantitative T2 imaging was found to provide an effective, nonsubjective means of classifying cervical anatomy and neo-plastic disease.     

Time after excision and temperature alter ex vivo tissue relaxation time measurements

Previously unreported effects of tissue storage were recently observed in the authors' experimental magnetic resonance (MR) studies. To evaluate the effect of elapsed time after excision and storage temperature on tissue relaxation time measurements, tissue samples from the liver, pancreas, kidney, testis, spleen, and brain were obtained in rats. T1 and T2 were first measured within 5 minutes of excision, and between subsequent measurements, tubes were kept in a water bath at 40°C, at room temperature (28°C), or in an ice bath (4°C). Cellular and organellar integrity was assessed with electron microscopy and correlated with the MR findings. At 40°C (20-MHz spectrometer), the T1 of liver decreased from 280 msec ± 8 to 212 msec ± 10 during the first 60 minutes; the T1 of pancreas decreased from 276 msec ± 3 to 208 msec ± 2. Other tissues showed less than a 5% decrease in T1. T2 changes were smaller than T1 changes in all tissues. Electron microscopy of pancreatic acinar cells showed postmortem changes in mitochondria evolving over the first 60 minutes after death. Manganese loading experiments implicated mitochondrial manganese stores in the observed enhanced postmortem decrease in T1. This study calls into question reported relaxation time data for liver and pancreas. MR studies of excised tissues must account for time and temperature to prevent systematic experimental errors.     

MR microscopy at 7.0 T: effects of brain iron.

The T2 of brain tissue is known to be field dependent, decreasing as B0 increases. Previous studies have attributed reduced T2 in the structures of the extrapyramidal motor system (EPMS) to high iron concentrations. The present study was designed to manipulate physiologic iron concentrations and study the effects on T2 and on the field dependence of T2 at 7.0 T in whole formalin-fixed brains. A rat model was devised in which iron concentrations in the structures of interest were altered by diet manipulation. Cerebral structures with different iron content were imaged and T2 measured with MR microscopy at both 2.0 and 7.0 T. T2 of all tissues was shorter by 40%-60% at 7.0 T. Although some dependence of T2 on iron concentration was evident, it was less than expected. The strongest correlation was in the substantia nigra. The highest-resolution studies, at 30 x 30 x 50 microns, show the myelin bundles in many of the EPMS structures but not in the substantia nigra. From these data, it appears that T2 at greater field strengths depends more on susceptibility-induced spin dephasing imposed by diffusion through the tissue microstructure than on the presence of iron.     

Localized proton MR spectroscopy of the brain in children

Small-voxel (3.0–8.0 cm³), magnetic resonance (MR) imaging–guided proton MR spectroscopy was performed in 54 patients (aged 6 days to 19 years) with intracranial masses (n = 16), neurodegenerative disorders (n = 34), and other neurologic diseases (n = 4) and in 23 age-matched control subjects without brain disease. A combined short TE (18 msec) stimulatedecho acquisition mode (STEAM) and long TE (135 and/or 270 msec) spin-echo point-resolved spatially localized spectroscopy (PRESS) protocol, using designed radio-frequency pulses, was performed at 1.5 T. STEAM spectra revealed short T2 and/or strongly coupled metabolites; prominent resonances were obtained from N-acetyl aspartate (NAA), choline-containing compounds (Cho), and total creatine (tCr). Lactate was well resolved with the long TE PRESS sequence. Intracranial tumors were readily differentiated from cerebrospinal fluid (CSF) collections. All tumors showed low NAA, high Cho, and reduced tCr levels. Neurodegenerative disorders showed low or absent NAA levels and enhanced mobile lipid, glutamate and glutamine, and inositol levels, consistent with neuronal loss, gliosis, demyelination, and amino acid neuro-toxicity. Preliminary experience indicates that proton MR spectroscopy can contribute in the evaluation of central nervous system abnormalities of infants and children.     

Magnetic resonance elastography of the human brain: a preliminary study

Purpose: To study the application of magnetic resonance elastography (MRE) in the human brain.

Material and Methods: An external force actuator was developed, which produced propagating shear waves in brain tissue. A modified phase-contrast gradient-echo sequence was developed. The propagating shear waves within the brain were directly imaged. The wave images were processed to obtain the elasticity image. Shear waves at 100 Hz, 150 Hz, and 200 Hz were applied.

Results: The propagating shear waves in the brain were visualized on wave images. The elasticity image revealed the difference in tissue elasticity between gray and white matter of the brain.

Conclusion: MRE could be an imaging technique for assessing the elasticity of brain tissue.     

Correlation of microvascular permeability derived from dynamic contrast-enhanced MR imaging with histologic grade and tumor labeling index: a study in human brain tumors

RATIONALE AND OBJECTIVES: Dynamic contrast material-enhanced magnetic resonance (MR) imaging may be used to quantify fractional blood volume (fBV) and microvascular permeability in human brain tumors. Hypothesis is that these measurements correlate with tumor histologic grade and immunohistologically assessed mitotic activity. MATERIALS AND METHODS: Thirty-eight patients with newly diagnosed gliomas underwent MR imaging consisting of dynamic three-dimensional spoiled gradient-recalled acquisition in the steady state image sets following bolus injections of a single dose of gadodiamide. Signal intensity changes in blood and tissue were kinetically analyzed, yielding estimates of fBV and microvascular permeability (k). Tumor specimens were graded with the World Health Organization-II four-point grading score. MIB-1 immunohistochemical labeling (anti-Ki-67 monoclonal antibody) was performed in 22 patients to evaluate mitotic activity. RESULTS: Histologic study revealed nine grade 2, 14 grade 3, and 15 grade 4 tumors. fBV ranged from 0.4% to 24%, k from -0.4 to 31.4 mL/100 cm3 x min, and MIB-1 labeling indexes from 1.7% to 42.8%. Correlation to the tumor grade was highest for permeability (r = 0.73), followed by the MIB-1 index (r = 0.63), and fBV (r = 0.48). Correlation between k and MIB-1 index was strong (r = 0.84). There was no statistically significant difference between the fBV of any of the groups. Despite some overlap between the permeability values of specific tumors from different grades, differences were statistically significant. The MIB-1 index was significantly different between grades 3 and 4 but not between grades 2 and 3. CONCLUSION: Dynamic contrast-enhanced MR imaging allows noninvasive determination of tumor fBV and microvascular permeability k. k is more reliable than the MIB-1 labeling index for differentiating grade 2 from grade 3 tumors.     

Quantitative MR relaxometry study of muscle composition and function in duchenne muscular dystrophy

Magnetic resonance imaging and maps of T1 and T2 values were used to study muscle composition in Duchenne muscular dystrophy (DMD). The mean T2 of anterior tibial muscle was 27 msec in healthy control subjects and 43 msec with increased fatty infiltration in DMD patients. In stronger DMD patients, the distribution of muscle T2 values was narrow, centered at 27 msec as in the controls, with a nonoverlapping fat peak centered at 49 msec. In weaker DMD patients, the width of the muscle T2 peak increased and the peak shifted toward the fat peak. Mean muscle T1 decreased from 1.7 to 0.6 second with increasing fatty infiltration. These results show that quantitative T1 and T2 maps may be used to assess muscle status and monitor DMD progression.     

Flip angle dependence of experimentally determined T1sat and apparent magnetization transfer rate constants

The purpose of this work was to develop a method for determining the T1_sat and magnetization transfer (MT) rate constants by analyzing the slice-select flip angle dependent MT behavior of normal white and gray matter. The technique uses a high MT power, three-dimensional (3D) gradient-recalled echo (GRE) sequence, with a well chosen MT pulse frequency offset, such that the experimental conditions closely satisfy requisite assumptions for invoking a first order rate process for MT. Integral to this method is that the T1_sat and MT ratio values are obtained under explicitly identical MT saturation conditions. The T1_sat of white matter was found to be approximately 300 msec, and the MT rate constant was approximately 2.0 sec^?1. The T1_sat of gray matter was approximately 500 msec, and the MT rate constant was 1.1 sec^?1. We also found a strong dependence of the MT rate constant on the slice-select flip angle used for the imaging sequence, independent of the MT saturation parameters. Strongly T1-weighted imaging sequences can result in the underestimation of the MT rate constant by 50%. Practical technical suggestions for quantitative MT experiments are put forth.     

In vivo relationship between marrow T2* and trabecular bone density determined with a chemical shift-selective asymmetric spin-echo sequence.

Magnetic field inhomogeneities due to differences in susceptibility between trabecular bone and bone marrow result in a reduction in T2*. The authors previously quantified the relationship between the relaxation rate enhancement per unit change in bone density, delta R2*, using dried, excised vertebral bodies immersed in saline. In the present study, they investigated the precision and reproducibility of such measurements in vitro and found that the short-term precision ranges from 2% to 11%, while the long-term precision error, which may be governed by the placement of the region of interest, can vary up to 50%. A chemical shift-selective asymmetric spin-echo sequence was used to assess T2* changes in the saturated fat component of bone marrow in vivo. It was shown that the marrow fat relaxation rate increases as the surrounding trabecular bone density increases and that the delta R2* of the marrow fat component was 0.20 sec-1/mg/cm3. The results also indicate that the distribution of T2* varies with image resolution. Both in vitro and in vivo, characteristics of the relaxation time distribution such as the mean, standard deviation, and skewness decrease as image resolution decreases, the degree of variation depending on the density of the surrounding trabecular network.     

Change in red blood cell relaxation with hydration: application to MR imaging of hemorrhage.

T1 and T2 were measured in unclotted blood samples with 0.24- and 4.7-T spectrometers. The fraction by weight of intracellular water in the red blood cells (RBCs) was varied by either osmotic manipulation or density separation in concentrated (packed RBCs) and dilute (RBCs suspended in buffer or serum) samples. Reducing the cell water content caused a moderate decrease in T1 and a profound decrease in T2 at both 0.24 and 4.7 T. Conversely, increasing the cell water content caused an increase in both T1 and T2. The authors conclude that dehydrated RBCs in an area of hemorrhage would cause a substantial decrease in signal intensity on long TR/TE (T2-weighted) images. Overhydration of RBCs would have the opposite effect.     

Proton magnetic resonance spectroscopy ((1)H MRS) of human brain tumours: assessment of differences between tumour types and its applicability in brain tumour categorization

Our objective was to evaluate the usefulness of proton magnetic resonance spectroscopy (¹H MRS) in categorizing brain tumours. In vivo single-voxel ¹H MRS at an echo time of 136 ms was performed in 108 patients with brain neoplasms that included 29 meningiomas (MEN), 15 low-grade astrocytomas (LGA), 12 anaplastic astrocytomas (AA), 25 glioblastomas (GBM) and 27 metastases (MET). Time-domain fitted areas of nine resonances were evaluated in all spectra. Twenty-five additional tumours were prospectively included as independent test set. Differences in at least two resonances were found in all pairwise comparisons of tumour groups except in GBM vs MET. Large lipid resonance at 1.30 ppm was found to be characteristic of GBM and MET, and alanine was characteristic of MEN. Significant differences were found between LGA and AA in choline-containing compounds and total creatine resonances. When implemented in a stepwise algorithm, these findings correctly classified 84% (21 of 25) tumours in the independent test set. Some additional utility was found in glycine/myo-inositol at 3.55 ppm for bilateral differentiation between GBM and MET (9 of 11, 82% correct classification in the test set). ¹H MRS provides useful information to categorize the most common brain tumours that can be implemented in clinical practice with satisfactory results. Electronic Publication     

T1rho MR imaging of the human wrist in vivo

RATIONALE AND OBJECTIVES: The purpose of this study was (a) to demonstrate the feasibility of computing T1rho maps of, and T1rho dispersion in, human wrist cartilage at MR imaging in vivo and (b) to compare T1rho and T2 weighting in terms of magnitude of relaxation times and signal intensity contrast. MATERIALS AND METHODS: T2 and T1rho magnetic resonance images of wrist joints in healthy volunteers (n = 5) were obtained with a spin-echo sequence and a fast spin-echo sequence pre-encoded with a spin-lock pulse cluster. A 1.5-T clinical imager was used (Signa; GE Medical Systems, Milwaukee, Wis) with a 9.5-cm-diameter transmit-receive quadrature birdcage coil tuned to 63.75 MHz. RESULTS: T1rho relaxation times at a spin-lock frequency of 500 Hz vary from 40.5 msec +/- 0.85 to 56.6 msec +/- 4.83, and T2 relaxation times vary from 28.1 msec +/- 1.88 to 34.5 msec +/- 2.63 (mean +/- standard error of the mean, n = 5, P < .016) in various regions of the wrist. T1rho dispersion was observed in the range of spin-lock frequencies studied. T1rho-weighted images not only have higher signal-to-noise ratios but also show better fluid and fat signal suppression than T2-weighted images. CONCLUSION: It was possible to perform T2- and T1rho-weighted MR imaging of human wrist cartilage in vivo with standard clinical imagers. The higher signal-to-noise ratio and improved contrast between cartilage and surrounding fat achieved with T1rho imaging may provide better definition of lesions and accurate quantitation of small changes in cartilage degeneration.     

MR imaging and proton spectroscopy of the brain in posttraumatic cortical blindness

Magnetic resonance (MR) imaging and localized proton MR spectroscopy of the occipital lobes were performed in a patient with cortical blindness following brain trauma. Computed tomography (CT) scans and MR images of the visual cortex were normal in the acute stage. Six weeks after the trauma, MR images showed cortical lesions in both occipital lobes, while the spectra showed elevated lactate and decreased N-acetyl aspartate levels relative to those of healthy volunteers. One year later, visual acuity had improved and follow-up studies revealed an increase in the ratios of N-acetyl aspartate to choline and creatine. These results demonstrate that parenchymal lesions may develop in brain regions that appear normal at CT and MR imaging during the acute stage after trauma. Metabolic changes can be observed in these areas by means of localized proton MR spectroscopy.     

T1, T2, and concentrations of brain metabolites in neonates and adolescents estimated with H-1 MR spectroscopy

The protein and lipid content of the human brain increases dramatically from infancy to adolescence. The authors investigated whether this change influences the relaxation behavior of metabolites measurable with hydrogen-1 magnetic resonance (MR) spectroscopy. H-1 MR spectroscopy was performed in eight neonates and eight adolescents at 1.5 T with STEAM (stimulated-echo acquisition mode) sequences. Five spectra were obtained in each volume of interest with different TE and TR values. T1 and T2 were subsequently calculated. T1 and T2 for inositols, choline-containing compounds (Cho), phosphocreatine plus creatine (PCr + Cr), and N-acetylaspartate (NAA) did not differ significantly between the two subject groups. Metabolite concentrations were estimated by using the fully relaxed water signal as an internal standard. Mean estimated concentrations of NAA and PCr + Cr were higher in the adolescent group, whereas the concentration of Cho was lower. The concentration of inositols was similar in the two groups.     

In vivo fluorine-19 MR imaging: Relaxation enhancement with Gd-DTPA

The lack of a naturally occurring background signal from fluorine in magnetic resonance (MR) imaging makes fluorinated compounds potentially attractive candidates for tissue-specific MR contrast agents. Problems associated with the in vivo use of fluorinated compounds are toxicity, which limits the amount of agent that can be used; multiple resonance lines; and an excessively long T1, which leads to long sequence TRs and consequently long imaging times. Many fluorinated agents also possess complex MR spectra that result in chemical shift artifacts if not corrected. The authors demonstrate the use of an extracellular fluorinated agent with a single MR peak for selective imaging of a brain abscess in an animal model and show that the image signal per unit of acquisition time can be enhanced through the use of a T1 relaxation agent, gadolinium diethylenetriamine-pentaacetic acid (DTPA). Trifluoromethylsulfonate was administered at a fluorine-19 dose of 4 mmol/kg, and fluorine images of the induced abscess were acquired before and after the injection of a standard dose of Gd-DTPA (0.1 mmol/kg); non—section-selected projection images were used. Typical imaging times were less than 5 minutes. The signal enhancement factor achieved was approximately four (4.0 ± 0.8) with use of a 500/12 (TR msec/TE msec) spinecho sequence.     

Multiparametric display of spin-echo data from MR studies of brain

A magnetic resonance (MR) image processing technique that uses a single color image for simultaneous presentation of spin-echo information and its application to MR studies of the brain is described. Relaxation rate and proton-density maps were calculated from 160 brain MR studies performed at 1.5 and 1.0 T with standard spin-echo sequences. Maps were fused into single color images, with R1, R2. and proton density coded, respectively, by red, green, and blue. The possibility of standardizing the technique was evaluated. Comparative analysis of color and conventional MR images of white matter disease and brain tumors was performed to assess intra- and interob-server variability. Unequivocal and reproducible chromatic characterization of normal brain structures and a variety of lesions was obtained. Intra-and interobserver analysis showed that color images can be used as a diagnostic tool. The technique may provide a simplified and timesaving approach for interpretation and presentation of brain MR studies.