More than meets the eye: significant regional heterogeneity in human cortical T1.

Segmented k-space acquisition of data was used to decrease the acquisition time and to increase the imaging resolution of the precise and accurate inversion recovery (PAIR) method of measuring T(1). We validated the new TurboPAIR method by measuring T(1) in 158 regions of interest in 12 volunteers, using both PAIR and TurboPAIR. We found a 3% difference between methods, which could be corrected by linear regression. After validation, the TurboPAIR method was used to test a hypothesis that there is significant regional heterogeneity in cortical T(1). We measured cortical gray matter T(1) in 11 right-handed volunteers, in 48 regions of interest scattered over frontal and parietal cortex, and in 46 ROIs along the central sulcus (CS). We found that T(1) in the CS is less than T(1) elsewhere in the cortex (p<0.001), and that there is considerable hemispheric asymmetry in T(1) in gray matter, but not in white matter. In central gray structures (caudate, thalamus, nucleus pulvinarus), and in the posterior CS (sensory cortex), right hemisphere T(1) was significantly greater than left hemisphere T(1) (p< or =0.004). In cortical gray matter of the frontal lobe and anterior CS (motor cortex), left hemisphere T(1) was significantly greater than right hemisphere T(1) (p< or =0.003). These findings demonstrate that there is considerable regional heterogeneity in human cortical T(1) that is unexplained by differences in tissue iron content, but may be evidence of an inherent anatomic asymmetry of the brain.

Age-related changes in brain T1 are correlated with iron concentration.

Age-related changes in brain T1 from 115 healthy subjects (range, 4.5-71.9 yr) were analyzed in relation to published regional brain iron concentration in cortex, caudate, putamen, and frontal white matter. The relaxation rate in these structures was linear with respect to iron concentration (P < 0.001). The iron relaxivity, k1 (s(-1)/mg iron/g wet weight), was much higher in cortex (5.5) and white matter (6.1) than in caudate (1.7) and putamen (1.0). These results are consistent with evidence that iron is an important factor in determining the relaxation properties of brain tissue. Iron relaxivity may reflect regional differences in the physical state of brain iron or in the interaction of brain iron with tissue water.

Quantitative MR imaging of children with sickle cell disease: striking T1 elevation in the thalamus.

Nineteen patients with sickle cell disease (SCD) were examined with conventional MR imaging (cMRI), including T1- and T2-weighted sequences and MR angiography (MRA). qMRI mapping of T1 was also done using a precise and accurate inversion-recovery (PAIR) technique optimized and validated previously. In addition, 21 healthy African-American control subjects had the qMRI examination. Nonparametric Kruskal-Wallis analysis of variance of control subjects, of SCD patients without stroke, and of SCD patients with stroke showed that T1 increased with disease severity in the thalamus, frontal white matter, genu, and occipital white matter. T1 was significantly longer in SCD patients without stroke (n = 13) than in control subjects (n = 21) in the thalamus and frontal white matter. In addition, T1 values were significantly longer in SCD patients with stroke than in patients without stroke in the genu and frontal white matter. Abnormality of the thalamus was identified by qMRI in a substantial fraction of patients read as normal by both cMRI and MRA, suggesting that it may be possible to use T1 elevation to identify a subset of patients with SCD who are at elevated risk for stroke.

Precise and accurate measurement of proton T1 in human brain in vivo: validation and preliminary clinical application.

Precise and accurate inversion-recovery (PAIR) magnetic resonance (MR) measurements of T1 were obtained in eight brain regions and cerebrospinal fluid of 26 healthy volunteers. Accuracy of the technique was assessed by measuring T1 in small fluid volumes with the PAIR technique and with two independent spectroscopic techniques. The mean difference between T1 measured with PAIR and with the two spectroscopic techniques was 3.1% +/- 1.3. The precision (reproducibility) of measurements with the PAIR technique was excellent. The coefficient of variation (CV) across 16 measurements in a head phantom was 2.0%, compared with a CV of 2.7% across 45 separate measurements in a single subject. The within-subject CV was 1.8% +/- 0.6 in white matter and 1.4% +/- 1.0 in basal ganglia. The between-subject CV in 26 healthy volunteers was 3.6% +/- 0.6 in white matter and 4.1% +/- 1.9 in basal ganglia. Comparison between a patient with an active recurrent brain tumor and an age-matched patient with an inactive brain tumor showed that T1 was significantly elevated throughout the brain of the active-tumor patient, especially in white matter tracts, even though no tumor or edema was detected in the white matter on standard MR images. Comparisons between five brain tumor patients and four healthy volunteers of similar age showed that T1 was significantly and substantially elevated throughout the white matter tracts and in the caudate nucleus, putamen, and thalamus. These results are consistent with the hypothesis that white matter tracts are selectively vulnerable to edema and that T1 increases in white matter are a sensitive indicator of patient status or tumor aggressiveness.

In vivo phosphorus NMR spectroscopy of skin using a crossover surface coil.

A modified crossover surface coil with minimal B1 field penetration was used for collection of skin phosphorus NMR spectra. Projection imaging experiments show that the coil-sensitive volume is uniform at the phosphorus frequency, but strikingly nonuniform at the proton frequency. Experiments with an in vitro phosphorus phantom, designed to simulate skin and underlying tissue, demonstrated that 45.1% (+/- 1.2%) of total signal was derived from Sprague-Dawley rat skin and 19.3% (+/- 1.4%) of total signal was derived from Fischer-344 rat skin. 31P MR spectra of rat skin in vivo permitted resolution of four phosphorus compounds: nucleoside triphosphates, phosphocreatine (PCr), inorganic phosphate (Pi), and phosphomonoester. Spectra collected after skin flap surgery in Fischer-344 rats showed a 50.1% (+/- 7.6%) reduction in the ratio of PCr/Pi within 30 min of surgery, compared to presurgical PCr/Pi levels (P less than 0.01). Skin phosphorus spectra are potentially useful for assessment of skin flap and skin graft viability.

31P NMR spectroscopic study of bioenergetic changes in radiation-induced fibrosarcoma-1 after radiation therapy.

The effects of localized gamma-irradiation on the in vivo 31P NMR spectra of RIF-1 tumors grown subcutaneously in C3H/HeN mice have been examined before and during the week after treatment. Increases in the ratio of phosphocreatine (PCr) to inorganic phosphate (Pi) and in tumor pH, and decreases in the ratio of Pi to the beta phosphorus resonance of the nucleotide triphosphates (beta NTP) were observed in irradiated tumors. The time course of changes in the 31P spectrum following treatment was the opposite of the pattern during untreated growth, and the magnitude and duration of the changes increased with increasing radiation dose, decreasing clonogenic cell survival and increasing growth delay. To examine the possibility that nontherapeutic systemic effects of the tumor irradiation were responsible for the changes observed, a number of animals bearing two tumors were examined. One tumor on each mouse was selectively irradiated. Changes in tumor volume, Pi/beta NTP, PCr/Pi, the ratio of phosphomonoesters to beta NTP, and tumor pH were all significantly different in the treated compared to the untreated tumor on each animal, indicating that these changes in 31P NMR spectra were a response to radiation therapy and not a systemic response to radiation toxicity.

In vivo 31P nuclear magnetic resonance spectroscopy of subcutaneous 9L gliosarcoma: effects of tumor growth and treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea on tumor bioenergetics and histology.

In vivo 31P nuclear magnetic resonance spectroscopy was used to examine the bioenergetics of the rat 9L gliosarcoma during untreated growth and in response to chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea. Tumor growth was associated with a decline in the phosphocreatine and nucleoside triphosphate resonances, consistent with an increase in tumor hypoxia during untreated growth. Following chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea (10 mg/kg), tumor levels of phosphocreatine and nucleoside triphosphate rebounded while the level of inorganic phosphate in the tumor declined. Histological comparison of treated and untreated tumor sections 4 days posttreatment showed that the treated tumor had a lower proportion of necrotic cells, a higher proportion of viable cells, and a 5-fold higher level of interstitial space than the control tumor.