Sensitivity calibration with a uniform magnetization image to improve arterial spin labeling perfusion quantification

Quantification of perfusion with arterial spin labeling MRI requires a calibration of the imaging sensitivity to water throughout the imaged volume. Since this sensitivity is affected by coil loading and other interactions between the subject and the scanner, the sensitivity must be calibrated in the subject at the time of scan. Conventional arterial spin labeling perfusion quantification assumes a uniform proton density and acquires a proton density reference image to serve as the calibration. This assumption, in the form of an assumed constant brain‐blood partition coefficient, incorrectly adds inverse proton density weighting to the perfusion image. Here, a sensitivity calibration is proposed by generating a uniform magnetization image whose intensity is highly independent of brain tissue type. It is shown that such a uniform magnetization image can be achieved, and brain tissue perfusion values quantified with the sensitivity calibration agree with those quantified with a proton density image when segmentation of brain tissues is performed and appropriate partition coefficients are assumed. Quantification of brain tissue water density is also demonstrated using this sensitivity calibration. This approach can improve and simplify quantification of arterial spin labeling perfusion and may have broader applications to measurement of edema and sensitivity calibration for parallel imaging. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.     

NMR in experimental cerebral edema: value of T1 and T2 calculations

In an experimental investigation, the efficacy of nuclear magnetic resonance (NMR) relaxation times in measuring brain water was studied. Cerebral edema was induced in four dogs with a freeze lesion, which was produced by contact with a steel cylinder cooled in liquid nitrogen and placed on the exposed dural surface of the brain. NMR proton imaging was performed 2, 3, 6, or 24 hr after production of the lesion, at a field strength of 0.35 T, using multiparametric spin-echo (SE) technique. The animals were sacrificed immediately after imaging, and brain samples were analyzed for water content (wet-to-dry, microgravimetry). Correlation between water content, NMR imaging, and resulting T1, T2 relaxation times and mobile proton density values calculated with SE technique was performed. Brain sample analysis showed elevation of water content in the white matter subjacent to the lesion in all four dogs, rising at least 15% in each of the animals. NMR imaging detected the freeze lesion and subjacent vasogenic edema of the white matter in all animals. The 2 sec pulse interval SE technique was most sensitive in the detection of the abnormality, and provided optimal differentiation of gray and white matter. The second echo sampling (56 msec) was most sensitive to the detection of edema. The T1 and T2 relaxation values, as well as the mobile proton density values, were elevated in the normal gray matter and in the abnormal white matter when compared with normal white matter in any given animal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Peritumoral brain edema in intracranial meningiomas evaluated by dynamic perfusion-weighted MR imaging: a preliminary study

Our objective was to semi-quantitatively evaluate the cerebral perfusion in the peritumoral brain edema of meningiomas using dynamic perfusion-weighted MR imaging. Six patients with intracranial meningiomas accompanied by peritumoral brain edema were prospectively examined by perfusion-weighted MR imaging. One patient was examined twice, once before and once 5 months after the surgical resection. The relative regional cerebral blood volume (rrCBV), the relative regional cerebral blood flow (rrCBF), and the relative regional mean transit time (rrMTT) were calculated for peritumoral brain edema and the contralateral white matter. These parameters were compared between peritumoral brain edema and the contralateral white matter. The time–concentration curve of the peritumoral brain edema was less prominent than that of the contralateral white matter, resulting in a significantly lower rrCBV (mean 46%) and rrCBF (mean 45%) in peritumoral brain edema than those of contralateral white matter. The serial perfusion-weighted MR imaging also demonstrated the recovery of these parameters after the removal of meningioma by means of surgical resection. Perfusion-weighted MR imaging can demonstrate significantly decreased rrCBV and rrCBF in peritumoral brain edema compared with those in normal white matter. Electronic Publication     

Physiologic changes in regional cerebral blood flow defined by xenon-enhanced CT scanning

Summary With adequate concentrations of commercially available nonradioactive xenon an enhancement of brain substance was readily demonstrated by computed tomography (CT). By performing successive CT scans at a fixed brain level following xenon inhalation, the partition coefficient and clearance of xenon as well as the regional cerebral blood flow (rCBF) could be calculated. The expected physiologic alterations in rCBF with acute cerebral infarction and changes in arterial CO₂ were accurately defined by xenon-enhanced CT scanning affirming the potential future applications of this technique.     

Cerebral gliomas: prospective comparison of multivoxel 2D chemical-shift imaging proton MR spectroscopy,echoplanar perfusion and diffusion-weighted MRI

Developments in MRI have made it possible to use diffusion-weighted MRI, perfusion MRI and proton MR spectroscopy (MRS) to study lesions in the brain. We evaluated whether these techniques provide useful, complementary information for grading gliomas, in comparison with conventional MRI. We studied 17 patients with histologically verified gliomas, adding multivoxel proton MRS, echoplanar diffusion and perfusion MRI the a routine MRI examination. The maximum relative cerebral blood volume (CBV), minimum apparent diffusion coefficient (ADC) and metabolic peak area ratios in proton MRS were calculated in solid parts of tumours on the same slice from each imaging data set. The mean minimum ADC of the 13 high-grade gliomas (0.92+/-0.27 x 10(-3) mm(2)/s) was lower than that of the four low-grade gliomas (1.28+/-0.15 x 10(-3) mm(2)/s) ( P<0.05). Means of maximum choline (Cho)/N-acetylaspartate (NAA), Cho/creatine (Cr), Cho/Cr in normal brain (Cr-n) and minimum NAA/Cr ratios were 5.90+/-2.62, 4.73+/-2.22, 2.66+/-0.68 and 0.40+/-0.06, respectively, in the high-grade gliomas, and 1.65+/-1.37, 1.84+/-1.20, 1.61+/-1.29 and 1.65+/-1.61, respectively, in the low-grade gliomas. Significant differences were found on spectroscopy between the high- and low-grade gliomas ( P<0.05). Mean maximum relative CBV in the high-grade gliomas (6.10+/-3.98) was higher than in the low-grade gliomas (1.74+/-0.57) ( P<0.05). Echoplanar diffusion, perfusion MRI and multivoxel proton MRS can offer diagnostic information, not available with conventional MRI, in the assessment of glioma grade.     

MRI abnormalities in normal-appearing brain tissue of treated adult PKU patients

PURPOSE: To detect possible subclinical pathological brain changes a study on adult phenylketonuria (PKU) patients by using quantitative MRI methods was performed, since neuropsychological and cognitive deficits in treated patients with PKU have not yet been shown to correlate clearly with the brain lesions identified by conventional MRI. MATERIALS AND METHODS: Eight subjects, four PKU patients with well-documented dietary treatment and four age- and sex-matched adult controls, underwent MRI, including a triple echo sequence and a diffusion tensor imaging sequence. Brain maps of T2 relaxation time (T2), relative proton density (PD), and fractional anisotropy (FA) as well as apparent diffusion coefficient (ADC) were derived for each subject. T2, PD, FA, and ADC were measured in 22 predefined regions of gray matter (GM) and white matter (WM) on the corresponding maps, and compared with those of four age-matched healthy adult controls. RESULTS: In addition to a prolonged T2 value measured in affected WM, as expected, we observed a significant shortening of the T2 relaxation time and reduction of ADC in normal-appearing brain tissue and an increased proton density in both GM and WM of the patients. No differences were observed in FA values between controls and patients. CONCLUSION: Repeatedly reduced T2 relaxation time, ADC, and increased proton density without changes in FA indicate a higher cell-packing density in normal-appearing brain without changes in the directedness of fibers. These structural changes may be related to neuropsychological and cognitive deficits in treated PKU patients.     

Usefulness of diffusion/perfusion-weighted MRI in rat gliomas: correlation with histopathology

RATIONALE AND OBJECTIVES: Diffusion/perfusion-weighted MRI (DWI/PWI) can provide additional useful information in the diagnosis of patients with brain gliomas in a noninvasive fashion. However, the exact role of these new techniques is still undergoing evaluation. Our hypothesis was that DWI and PWI could be useful for assessment of growth and vascularity of implanted C6 rat gliomas. MATERIALS AND METHODS: Thirty-six rats were implanted with C6 glioma cells intracerebrally. Between 1 and 4 weeks after implantation, 8-10 rats were imaged on a clinical, 1.5-T whole-body magnetic resonance system with T(1)-weighted imaging (T(1)WI), T(2)-weighted imaging, DWI, PWI, and postcontrast T(1)WI at each weekly time point. All tumors were examined histologically; tumor cellularity and microvascular density were counted. RESULTS: On DWIs, statistical differences of apparent diffusion coefficient values for both the tumoral core and peritumoral region were present comparing tumors of 3-4 weeks' growth with tumors of 1-2 weeks' growth. Apparent diffusion coefficient value of tumoral core was negatively correlated with tumor cellularity (r = -0.682, P < .01). Statistical difference of maximal regional cerebral blood volume of tumoral core was present comparing 2-4 weeks with both 1 week after implantation and contralateral white matter (P < .01). Native vessel dilation in regions of normal brain at the periphery of the tumors at 1 week after implantation was observed. Correlation between maximal regional cerebral blood volume of tumor core and microvascular density was present (r = 0.716, P < .01). CONCLUSION: DWI and PWI has potential to characterize C6 gliomas in rats, which is a promising model similar to human gliomas.     

A fast technique to estimate local cerebral blood flow and partition coefficient using dynamic PET of H(2)15O: a new approach to weighted integration method based on time integration of Kety-Schmidt equation

We developed a new technique for fast estimation of local cerebral blood flow and partition coefficient based on time integration of Kety-Schmidt equation. This technique has two advantages concerning statistical noise. Firstly, it does not need a Ci(T) image which contains high statistical noise because of low activity in brain. Secondly, statistical noise is minimized by time integration of Kety-Schmidt equation before multiplied by weighting function. The error analyses in flow and partition coefficient caused by statistical noise were performed using computer simulation, and dynamic PET human study using H(2)15O bolus injection. Both simulation and PET study indicated that uncertainties of flow and partition coefficient were confirmed to be lower in this technique than in the original weighted integration method.     

Mapping of local cerebral blood flow with stable xenon-enhanced CT and the curve-fitting method of analysis

A noninvasive method is described for estimating local cerebral blood flow (LCBF) and local partition coefficients by means of computed tomographic scanning during inhalation of 30% stable xenon gas in oxygen. Time-dependent xenon concentrations in arterial blood and brain tissue during the wash-in and washout phases are used to calculate partition coefficients and LCBF values by means of a least-squares curve-fitting analysis. Control values for partition coefficient and LCBF obtained from control subjects with minor head trauma in the chronic stage were compatible with those in several past reports, and reproducibility was satisfactory. The theoretic grounds underlying this new method of curve-fitting analysis are discussed.     

Method for quantitative imaging of the macromolecular 1H fraction in tissues.

A new method was developed for mapping the relative density of the macromolecular protons involved in magnetization transfer (MT). This method employs a stimulated echo preparation scheme in order to modulate the phase distribution within a spin ensemble. This labeled spin ensemble is then used as an intrinsic indicator, which is diluted due to magnetization exchange with macromolecular protons. A pulse sequence is presented which compensates for longitudinal relaxation, allows observation of the dilution effect only, and provides for calculation of parameter maps using indicator dilution theory. Compared to other quantitative MT techniques, neither additional relaxation time measurements nor knowledge regarding the lineshape of the macromolecular proton pool are required. Moreover, the inherent low specific absorption rate and the low sensitivity for B(1) errors make this method favorable in a clinical setting. This sequence was used to measure the macromolecular proton density in cross-linked bovine serum albumin. Using a navigated echo planar readout, the sequence was also employed to visualize the macromolecular content of human brain in vivo.     

Sturge-Weber syndrome: diffusion magnetic resonance imaging and proton magnetic resonance spectroscopy findings

We report on the diffusion magnetic resonance imaging (MRI) and proton MR spectroscopy findings of a 26-year-old female patient with Sturge-Weber syndrome. Echo-planar trace diffusion MRI revealed mildly high signal intensity changes at parieto-occipital lobes on b = 1000 s/mm² images, suggesting restricted diffusion. On corresponding apparent diffusion coefficient maps, those areas had moderately high signal intensity and high apparent diffusion coefficient values (around 0.9×10(-3) mm²/s) compared with the contralateral symmetrical normal side of the brain (0.776×10(-3) mm²/s). This finding was consistent with increased motion of water molecules (disintegration of the neural tissue) in these regions. Proton MR spectroscopy revealed decreased N-acetyl aspartate and increased choline peaks, indicating disintegration of neural tissue associated with neuronal loss as well.     

Relationship between lipophilicity and brain extraction of C-11-labeled radiopharmaceuticals

The brain extraction of fifteen C-11-labeled compounds during a single capillary transit was studied in adult baboons by external detection of these tracers after injection into the internal carotid artery. The log Poct (partition coefficient for octanol/water) values of these compounds range from --0.7 to greater than 4.0. A parabolic relationship was found between the log Poct value of the C-11-labeled compounds and the fraction of the radiopharmaceutical entering the brain. Compounds with log Poct values between 0.9 and 2.5 were found to pass freely across the blood-brain barrier at a cerebral blood flow of 100 ml X min-1 X hg-1. An apparently decreased extraction of very lipophilic compounds was shown to be related to binding of the tracer to blood components and macromolecules (red blood cells, albumin, etc.). These data suggest that a radiopharmaceutical designed to measure blood flow should have a log Poct value of between 0.9 and 2.5.     

Intravoxel distribution of DWI decay rates reveals C6 glioma invasion in rat brain.

The hypothesis was tested that the intravoxel distribution of water diffusion rates, as measured with a stretched-exponential model of diffusion-weighted imaging (DWI), is a marker of brain tumor invasion. Eight rats underwent intracerebral inoculation of C6 glioma cells. In three rats, cells were labeled with a fluorescent dye for microscopy. One rat was inoculated with a saline solution, and five more rats were imaged without inoculation as controls. Five healthy uninoculated rats were also imaged. DWI was performed 14-15 days after inoculation, with diffusion-weighting factor b = 500 to 6500 sec/mm2, and the resulting signal attenuation was fitted with the stretched-exponential model. The heterogeneity index values were significantly lower (P < 0.05) in the peritumor ROI than in normal gray matter and significantly higher than in normal white matter. The distributed diffusion coefficient values were significantly lower than in normal white matter or normal gray matter. Fluorescence microscopy confirmed the presence of tumors in the peritumor region that could be histologically distinguished from the main tumor mass. There was no change in proton density or T2-weighted images in the peritumor region, making vasogenic edema unlikely as a source of contrast. It is therefore thought that the heterogeneity parameter alpha is a marker of brain tumor invasion.     

Use of proton beams with breast prostheses and tissue expanders

Since the early 2000s, a small but rapidly increasing number of patients with breast cancer have been treated with proton beams. Some of these patients have had breast prostheses or tissue expanders in place during their courses of treatment. Procedures must be implemented to plan the treatments of these patients. The density, kilovoltage x-ray computed tomography numbers (kVXCTNs), and proton relative linear stopping powers (pRLSPs) were calculated and measured for several test sample devices. The calculated and measured kVXCTNs of saline were 1% and 2.4% higher than the values for distilled water while the calculated RLSP for saline was within 0.2% of the value for distilled water. The measured kVXCTN and pRLSP of the silicone filling material for the test samples were approximately 1120 and 0.935, respectively. The conversion of kVXCTNs to pRLSPs by the treatment planning system standard tissue conversion function is adequate for saline-filled devices but for silicone-filled devices manual reassignment of the pRLSPs is required.     

Cerebral perfusion impairment correlates with the decrease of CT density in acute ischaemic stroke

Within the first 6 h of ischaemic stroke, changes on computed tomography (CT) scans are known as early ischaemic signs. We tested the hypothesis that the severity of perfusion impairment correlates with the degree of CT density decrease. Water uptake in ischaemic brain tissue results in a subtle decrease of CT density, and was quantified by delineation of the corresponding decrease of the apparent diffusion coefficient (ADC). Regions of decreased ADC and CT density in 29 acute-stroke patients were superimposed on the corresponding magnetic resonance perfusion images. Mean values of ADC and CT density decrease were correlated with the corresponding relative changes of cerebral blood flow (rCBF) and volume (rCBV), mean transit time (rMTT) and time-to-peak (rTTP). The decrease of CT density was 1.2±0.6 Hounsfield units and showed a linear correlation with rCBF (0.42, p<0.01) as well as rCBV (0.62, p<0.01), but not with the prolongation of rMTT (1.43, p=0.78) or rTTP (1.34, p=0.26). Therefore, the reduction of rCBF determines the severity of the early ischaemic oedema (EIOE) on CT, as well as reduction of the ADC. These findings provide a coherent view on the pathophysiology of the EIOE.     

Perfusion MRI of U87 brain tumors in a mouse model.

Continuous arterial spin labeling (CASL) was used to obtain an index of cerebral blood flow (ICBF) in the normal mouse brain and in an orthotopic mouse model of human U87 high-grade glioma at 8.5 T. Under the assumption of a constant tissue:blood partition coefficient for water in different tissues, the mean ICBF (n = 14) was found to be 50 +/- 9 mL/100g/min for tumor core and 209 +/- 11 mL/100g/min for normal tissue. The apparent T(1) (T(1app)) was 2.01 +/- 0.06 sec for tumor core and 1.66 +/- 0.03 sec for normal tissue. The ICBF and the T(1app) values were significantly different (P < 0.001) between these two regions. The detailed changes of ICBF and T(1app) in the transition from the tumor core through the tumor periphery to surrounding tissue were studied. Immunohistochemistry indicated that tumor vascularity was not uniform, with microvessel density highest in normal brain and the tissue surrounding the tumor and lowest in the tumor core. The large difference in ICBF between the tumor core and normal tissue suggests that this index might be useful for the assessment of the efficacy of antiangiogenic therapy.     

Correction for vascular artifacts in cerebral blood flow values measured by using arterial spin tagging techniques

?Vascular”? artifacts can have substantial effects on human cerebral blood flow values calculated by using arterial spin tagging approaches. One vascular artifact arises from the contribution of ?tagged”? arterial water spins to the observed change in brain water MR signal. This artifact can be reduced if large bipolar gradients are used to ?crush”? the MR signal from moving arterial water spins. A second vascular artifact arises from relaxation of ?tagged”? arterial blood during transit from the tagging plane to the capillary exchange site in the imaging slice. This artifact can be corrected if the arterial transit times are measured by using ?dynamic”? spin tagging approaches. The mean transit time from the tagging plane to capillary exchange sites in a gray matter region of interest was calculated to be ～0.94 s. Cerebral blood flow values calculated for seven normal volunteers agree reasonably well with values calculated by using radioactive tracer approaches.     

Whole brain apparent diffusion coefficient histogram: a new tool for evaluation of leukoaraiosis

PURPOSE: To test whole brain apparent diffusion coefficient histogram analysis as an alternative approach to visual score for the assessment of leukoaraiosis (LA). MATERIALS and METHODS: T2 and diffusion weighted images were obtained in 15 elderly patients. LA extension was assessed on T2 weighted images by two observers using a semiquantitative visual score. Apparent diffusion coefficient (ADC) maps of the entire brain were generated and, after exclusion of the skull with manual tracing and of the cerebrospinal fluid (CSF) by application of a threshold value, whole brain (WB)-ADC histogram was obtained. Moreover, a brain volume index (BVI) was calculated on ADC maps as (intracranial volume - CSF volume) /intracranial volume. RESULTS: The kappa inter-observer agreement for LA scoring was 0.69. Manual segmentation of the skull showed a mean inter-operator coefficient of variation below 3%. The median value of whole brain ADC histogram directly correlated with LA extension (P = 0.013). Moreover a significant inverse correlation (P = 0.002) was found between WB-ADC median value and BVI. CONCLUSION: WB-ADC histogram is a reproducible alternative tool for assessing LA extension and severity.     

Thin-section MR imaging of rat brain at 4.7 T.

The brains of anesthetized 7-month-old male hooded rats were imaged in coronal, sagittal, and horizontal planes at 4.7 T. Images were obtained with a section thickness of 0.6 mm and in-plane pixel size of 0.18-0.20 mm, resulting in finer combined spatial and contrast resolution than in most previously published reports. This allowed detailed anatomic assignment of many brain structures on the basis of comparison with a histologic brain atlas. T1, apparent T2, and water proton density values of gray matter, white matter, and cerebrospinal fluid (CSF) were derived from saturation-recovery and multi-echo measurements. These values were used to calculate expected contrast-to-noise ratios as a function of TR and TE in spin-echo imaging sequences. The optimal simultaneous contrast between gray and white matter and between CSF and gray matter was obtained on images with moderate T2 weighing, with a TR of 3.6 seconds and a TE of 45 msec. The use of thin sections was found to be essential for resolving many fine structures, and the improved sensitivity provided by the high magnetic field strength was crucial for imaging such thin sections at adequate signal-to-noise ratios.     

Errors in the spleen-blood partition coefficient for water in C15O2 steady-state PET

The aim of this study was to clarify if the value of 0.93, determined for patients with normal livers, is useful as a pathological spleen-blood partition coefficient for water when the splenic blood flow is quantified by the C15O2 steady-state method. A steady-state PET scan with continuous inhalation of C15O2 and a dynamic PET scan with a H(2)15O bolus injection were performed. From 157 patients, 392 slices were chosen as having planes that encompassed the spleen and provided regions of interest with full signal imaging. A comparison of the results of the steady-state and dynamic methods was performed. When 0.93 was adopted as the spleen-blood partition coefficient for water, an error of about 25% was seen in the splenic blood flow of patients with cirrhosis. When measuring splenic blood flow, the H(2)15O dynamic method is necessary. However, a rough estimate of splenic blood flow is possible by the C15O2 PET steady-state method, if this error is known.