Evaluating the accuracy and precision of a two-compartment Kärger model using Monte Carlo simulations.

Specific parameters of the neuronal tissue microstructure, such as axonal diameters, membrane permeability and intracellular water fractions are assessable using diffusion MRI. These parameters are commonly estimated using analytical models, which may introduce bias in the estimated parameters due to the approximations made when deriving the models. As an alternative to using analytical models, a database of signal curves generated by fast Monte Carlo simulations can be employed. Simulated diffusion MRI measurements were generated and evaluated using the two-compartment Kärger model as well as the simulation model based on a database containing signal curves from approximately 60000 simulations performed with different combinations of microstructural parameters. A protocol based on a pulsed gradient spin echo sequence with diffusion times of 30 and 60 ms and with gradient amplitudes obtainable with a clinical MRI scanner was employed for the investigations. When using the analytical model, a major negative bias (up to approximately 25%) in the estimated intracellular volume fraction was observed for short exchange times, while almost no bias was seen for the simulation model. In general, the simulation model improved the accuracy of the estimated parameters as compared to the analytical model, except for the exchange time parameter.

Diffusion-weighted MRI measurements on stroke patients reveal water-exchange mechanisms in sub-acute ischaemic lesions.

The aim of this study was to investigate the diffusion time dependence of signal-versus-b curves obtained from diffusion-weighted magnetic resonance imaging (DW-MRI) of sub-acute ischaemic lesions in stroke patients. In this case series study, 16 patients with sub-acute ischaemic stroke were examined with DW-MRI using two different diffusion times (60 and 260 ms). Nine of these patients showed sufficiently large lesions without artefacts to merit further analysis. The signal-versus-b curves from the lesions were plotted and analysed using a two-compartment model including compartmental exchange. To validate the model and to aid the interpretation of the estimated model parameters, Monte Carlo simulations were performed. In eight cases, the plotted signal-versus-b curves, obtained from the lesions, showed a signal-curve split-up when data for the two diffusion times were compared, revealing effects of compartmental water exchange. For one of the patients, parametric maps were generated based on the extracted model parameters. These novel observations suggest that water exchange between different water pools is measurable and thus potentially useful for clinical assessment. The information can improve the understanding of the relationship between the DW-MRI signal intensity and the microstructural properties of the lesions.

Gadolinium contrast agent is of limited value for magnetic resonance imaging assessment of synovial hypertrophy in hemophiliacs.

PURPOSE: To examine the influence of different doses of gadolinium contrast agent on synovial enhancement, to compare magnetic resonance imaging (MRI) findings of synovial hypertrophy and radiographic joint changes in hemophiliacs, and to investigate the value of gadolinium in MRI assessment of synovial hypertrophy in hemophiliacs using dynamic MRI and MRI scoring. MATERIAL AND METHODS: Twenty-one hemophiliacs on prophylactic factor treatment without recent bleeds were subjected to radiography and gadolinium contrast-enhanced dynamic and static MRI of the knee using a standard dose of 0.1 mmol/kg b.w. gadoteridol. In 17 of the patients, the MRI procedure was repeated after a triple dose of gadoteridol. RESULTS: MRI findings of synovial hypertrophy were significantly correlated with Pettersson radiographic scores. In 19 of the 21 MRI investigated joints, administration of contrast agent did not alter the result of the evaluation of synovial hypertrophy. CONCLUSION: The optimal time interval for volume assessment of synovial hypertrophy after injection of gadolinium contrast agent is dose dependent. Hemophiliacs without recent bleeds have minor to abundant synovial hypertrophy in joints with pronounced radiographic changes. Dynamic MRI is not useful for evaluating hemophilic arthropathy, and gadolinium contrast agent is not routinely indicated for MRI scoring of joints in hemophiliacs.

Attempts to improve absolute quantification of cerebral blood flow in dynamic susceptibility contrast magnetic resonance imaging: a simplified T1-weighted steady-state cerebral blood volume approach.

BACKGROUND: Attempts to retrieve absolute values of cerebral blood flow (CBF) by dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) have typically resulted in overestimations. PURPOSE: To improve DSC-MRI CBF estimates by calibrating the DSC-MRI-based cerebral blood volume (CBV) with a corresponding T1-weighted (T1W) steady-state (ss) CBV estimate. MATERIAL AND METHODS: 17 volunteers were investigated by DSC-MRI and 133Xe SPECT. Steady-state CBV calculation, assuming no water exchange, was accomplished using signal values from blood and tissue, before and after contrast agent, obtained by T1W spin-echo imaging. Using steady-state and DSC-MRI CBV estimates, a calibration factor K = CBV(ss)/CBV(DSC) was obtained for each individual. Average whole-brain CBF(DSC) was calculated, and the corrected MRI-based CBF estimate was given by CBF(ss) = K x CBF(DSC). RESULTS: Average whole-brain SPECT CBF was 40.1+/-6.9 ml/min x 100 g, while the corresponding uncorrected DSC-MRI-based value was 69.2+/-13.8 ml/min x 100 g. After correction with the calibration factor, a CBF(ss) of 42.7+/-14.0 ml/min x 100 g was obtained. The linear fit to CBF(ss)-versus-CBF(SPECT) data was close to proportionality (R = 0.52). CONCLUSION: Calibration by steady-state CBV reduced the population average CBF to a reasonable level, and a modest linear correlation with the reference 133Xe SPECT technique was observed. Possible explanations for the limited accuracy are, for example, large-vessel partial-volume effects, low post-contrast signal enhancement in T1W images, and water-exchange effects.

Wavelet-based noise reduction for improved deconvolution of time-series data in dynamic susceptibility-contrast MRI.

Dynamic susceptibility-contrast (DSC) MRI requires deconvolution to retrieve the tissue residue function R(t) and the cerebral blood flow (CBF). In this study, deconvolution of time-series data was performed by wavelet-transform-based denoising combined with the Fourier transform (FT). Traditional FT-based deconvolution of noisy data requires frequency-domain filtering, often leading to excessive smoothing of the recovered signal. In the present approach, only a low degree of regularisation was employed while the major noise reduction was accomplished by wavelet transformation of data and Wiener-like filtering in the wavelet space. After inverse wavelet transform, the estimate of CBF.R(t) was obtained. DSC-MRI signal-versus-time curves (signal-to-noise ratios 40 and 100) were simulated, corresponding to CBF values in the range 10-60 ml/(min 100 g). Three shapes of the tissue residue function were investigated. The technique was also applied to six volunteers. Simulations showed CBF estimates with acceptable accuracy and precision, as well as independence of any time shift between the arterial input function and the tissue concentration curve. The grey-matter to white-matter CBF ratio in volunteers was 2.4+/-0.2. The proposed wavelet/FT deconvolution is robust and can be implemented into existing perfusion software. CBF maps from healthy volunteers showed high quality.

Perfusion assessment with bolus differentiation: a technique applicable to hyperpolarized tracers.

A new technique for assessing tissue blood flow using hyperpolarized tracers, based on the fact that the magnetization of a hyperpolarized substance can be destroyed permanently, is described. Assessments of blood flow with this technique are inherently insensitive to arterial delay and dispersion, and allow for quantification of the transit time and dispersion in the arteries that supply the investigated tissue. Renal cortical blood flow was studied in six rabbits using a 13C-labeled compound (2-hydroxyethylacrylate) that was polarized by the parahydrogen-induced polarization (PHIP) technique. The renal cortical blood flow was estimated to be 5.7/5.4 +/- 1.6/1.3 ml/min per milliliter of tissue (mean +/- SD, right/left kidney), and the mean transit time and dispersion in the renal arteries were determined to be 1.47/1.42 +/- 0.07/0.07 s and 1.78/1.93 +/- 0.40/0.42 s2, respectively.

Effects of echo time variation on perfusion assessment using dynamic susceptibility contrast MR imaging at 3 tesla.

The implications of changing the echo time of a gradient-echo echo planar imaging sequence applied to dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) for perfusion imaging at 3T were investigated. Four echo times in the range of 21 to 45 ms were examined in a total of 17 patients who received a dose of 0.1 mmol/kg bodyweight Gadobutrol (Gadovist, 1.0 mmol/ml). As the primary optimization parameter, the concentration-to-noise ratio (SNRc) was selected as it takes effects of variations in baseline as well as in signal drop into account. In an analysis of gray matter, white matter and arterial regions of interest, SNRc showed the highest values for the shortest applied echo time in all cases. Maps of regional cerebral blood volume (rCBV) and blood flow (rCBF) were calculated using deconvolution based on singular value decomposition. The quality of rCBF and rCBV images was judged to be good or excellent in all cases, independent of the echo time. Calculated gray matter/white matter ratios of rCBF and rCBV displayed no significant dependence on the applied echo time. Considering the better SNRc and arterial signal saturation aspects, we found that the shortest investigated echo time was the superior one. We thus suggest that short echo times should be applied, taking technical limitations and clinical demands into consideration.

Cerebral perfusion assessment by bolus tracking using hyperpolarized 13C.

Cerebral perfusion was assessed with 13C MRI in a rat model after intravenous injections of the 13C-labeled compound bis-1,1-(hydroxymethyl)-1-13C-cyclopropane-D8 in aqueous solutions hyperpolarized by dynamic nuclear polarization (DNP). Since the tracer acted as a direct signal source, several of the problems associated with techniques based on traditional dynamic susceptibility contrast (DSC) MRI contrast agents were avoided. Maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were calculated. The MTT was determined to be 2.8 +/- 0.8 sec. However, arterial partial-volume effects in the animal model prevented accurate absolute quantification of CBF and CBV. It was demonstrated that depolarization of the hyperpolarized 13C tracer via relaxation and the imaging sequence had little influence on CBF assessment when the time resolution of the imaging sequence was short compared to the MTT. However, CBV and MTT were increasingly underestimated as MTT or the depolarization rate increased if depolarization was not taken into account. With a modified bolus-tracking theory depolarization could be compensated for, assuming that the depolarization rate was known. Three separate compensation methods were investigated experimentally and by numerical simulations.

Hand-arm-vibration syndrome (HAVS): is there a central nervous component? An fMRI study.

Hand-held vibrating tools may result in neuromuscular dysfunction and vasospastic problems of the hand. Sensory and motor dysfunction can be explained by injury to peripheral structures, but could also be due to changes in cortical somatotopic mapping of the hand in the brain. The purpose of the present study was to use functional magnetic resonance imaging (fMRI) to assess the somatotopic cortical representation of the hands of workers subjected to occupational vibration. The study included six men with severe vibration exposures who were suffering from hand-arm-vibration syndrome (HAVS) and six controls. The analysis focused on the pattern and degree of activation of contra- and ipsilateral hemispheres of the brain with tactile stimulation and motor activation of the hand. These stimulations resulted in well-defined activation of the contralateral, and to a lesser extent the ipsilateral hemisphere. Statistical analysis of this limited patient material did not indicate any significant somatotopic cortical changes following long-term exposure to vibrating hand-held tools, although there was a tendency to a shift of activation towards the more cranial parts of the cortex in the patient group.

Gradient echo imaging of flowing hyperpolarized nuclei: theory and phantom studies on 129Xe dissolved in ethanol.

The influence of flip angle and flow velocity on the signal intensity achieved when imaging a hyperpolarized substance with a spoiled gradient echo sequence was investigated. The study was performed both theoretically and experimentally using hyperpolarized xenon dissolved in ethanol. Analytical expressions regarding the optimal flip angle with respect to signal and the corresponding signal level are presented and comparisons with thermally polarized substances are made. Both experimentally and theoretically, the optimal flip angle was found to increase with increasing flow velocity. Numerical calculations showed that the velocity dependence of the signal differs between the cases of hyperpolarized and thermally polarized substances.

Echo-planar MR imaging of dissolved hyperpolarized 129Xe.

PURPOSE: The feasibility of hyperpolarized 129Xe for fast MR angiography (MRA) was evaluated using the echo-planar imaging (EPI) technique. MATERIAL AND METHODS: Hyperpolarized Xe gas was dissolved in ethanol, a carrier agent with high solubility for Xe (Ostwald solubility coefficient 2.5) and long relaxation times. The dissolved Xe was injected as a bolus into a flow phantom where the mean flow velocity was 15 cm/s. Ultrafast EPI images with 44 ms scan time were acquired of the flowing bolus and the signal-to-noise ratios (SNR) were measured. RESULTS: The relaxation times of hyperpolarized Xe in ethanol were measured to T1=160+/-11 s and T2 approximately 20 s. The resulting images of the flowing liquid were of reasonable quality and had an SNR of about 70. CONCLUSION: Based on the SNR of the obtained Xe EPI images, it was estimated that rapid in vivo MRA with 129Xe may be feasible, provided that an efficient, biologically acceptable carrier for Xe can be found and polarization levels of more than 25% can be achieved in isotopically enriched 129Xe.

Variation in heritability of tadpole growth: an experimental analysis.

Heritability characteristically shows large variation between traits, among populations and species, and through time. One of the reasons for this is its dependence on gene frequencies and how these are altered by selection and drift through the evolutionary process. We studied variation in heritability of tadpole growth rate in populations of the Swedish common frog, Rana temporaria. In populations evolving under warmer conditions, we have demonstrated elsewhere that tadpoles show better growth and physiological performance at relatively higher temperatures than tadpoles with an evolutionary history in a relatively cooler part of the distribution range. In the current study, we ask whether this process of divergence under natural selection has influenced the genetic architecture as visualised in estimates of heritability of growth rate at different temperature treatments under laboratory conditions. The results suggest that the additive genetic variance varies between treatments and is highest in a treatment that is common to both populations. Our estimates of narrow sense heritability are generally higher in the thermal regime that dominates in the natural environment. The reason for this appears not primarily to be because the component of additive genetic variation is higher in relation to the total phenotypic variation under these conditions, but because the part of the phenotypic variance explained by environmental variation increases at temperatures to which the current populations has been less frequently under selection.

Simple bone cyst: a discrepancy between magnetic resonance imaging and surgical observations.

OBJECTIVE: The purpose of this study was to compare magnetic resonance (MR) imaging and surgical observations of fluid in simple bone cysts. STUDY DESIGN: Findings during MR imaging of 7 simple bone cysts were compared with surgical observations 1 day or 1.8 months (mean) after MR imaging. RESULTS: All MR images showed cavities filled with fluid. In 2 patients operated on the day after the imaging, surgical observations were in accordance with the MR findings. At surgery 1.8 months after the MR examination, 4 cavities were found to be empty and 1 cavity contained only a minor amount of fluid. CONCLUSION: A discrepancy between MR imaging and surgical observations of fluid in simple bone cyst cavities was observed that might be dependent on the time between the observations, indicating that a fairly rapid absorption of fluid might occur or that the amount of fluid in a simple bone cyst can vary for unknown reasons.

New views on RPE65 deficiency: the rod system is the source of vision in a mouse model of Leber congenital amaurosis.

Leber congenital amaurosis (LCA) is the most serious form of the autosomal recessive childhood-onset retinal dystrophies. Mutations in the gene encoding RPE65, a protein vital for regeneration of the visual pigment rhodopsin in the retinal pigment epithelium, account for 10-15% of LCA cases. Whereas previous studies of RPE65 deficiency in both animal models and patients attributed remaining visual function to cones, we show here that light-evoked retinal responses in fact originate from rods. For this purpose, we selectively impaired either rod or cone function in Rpe65-/- mice by generating double- mutant mice with models of pure cone function (rhodopsin-deficient mice; Rho-/-) and pure rod function (cyclic nucleotide-gated channel alpha3-deficient mice; Cnga3-/-). The electroretinograms (ERGs) of Rpe65-/- and Rpe65-/-Cnga3-/- mice were almost identical, whereas there was no assessable response in Rpe65-/-Rho-/- mice. Thus, we conclude that the rod system is the source of vision in RPE65 deficiency. Furthermore, we found that lack of RPE65 enables rods to mimic cone function by responding under normally cone-isolating lighting conditions. We propose as a mechanism decreased rod sensitivity due to a reduction in rhodopsin content to less than 1%. In general, the dissection of pathophysiological processes in animal models through the introduction of additional, selective mutations is a promising concept in functional genetics.

The value of b required to avoid T2 shine-through from old lucunar infarcts in diffusion-weighted imaging.

Multiple small infarcts of different ages are common in small-vessel disease. Diffusion-weighted imaging (DWI) is a powerful method for discriminating new from chronic lesions. This can be done on the diffusion-weighted images provided that b is sufficiently high. Our purpose was to determine that critical value of b. We reviewed DWI from a previous study of acute, mainly lacunar strokes, and selected 18 old lacunar infarcts, well defined on uncoded images with b 0 s/m2 (i. e., T2-weighted images) but invisible on DWI with b 1,200 x 10(6) s/m2. We used a 1.5 tesla imager and single-shot echo-planar technique. We had seven separate acquisitions with echo time 123 ms and b in steps between 0 and 1,200 x 10(6) s/m2. Two neuroradiologists blinded to the selection of lesions carried out two different lesion-detection procedures, thereby testing each lesion four times, giving a total of 72 tests of b values. The results were consistent, indicating a level for detection of 800 x 10(6) s/m2 in two tests, 400-600 x 10(6) s/m2 in 65 tests and at lower values in the remainder. For imagers up to 1.5 tesla, at long repetition times and an echo time up to 120 ms T2-shine through of old lacunar infarcts can be avoided using b of 1,000 x 10(6) s/m2.

Persistent high signal on diffusion-weighted MRI in the late stages of small cortical and lacunar ischaemic lesions.

Diffusion-weighted imaging (DWI) is very sensitive to early brain infarcts. However, the late stages have been insufficiently studied. Infarcts in small vessel disease are often multiple and of different ages, and differentiation between new and old lesions might be difficult. We have therefore studied the change with time in DWI of small (< 3 ml) ischaemic lesions. We imaged 21 patients with an acute lacunar syndrome and a lesion visible on early DWI. They all had three MRI examinations 12-58 h (early), 7-16 and 54-144 days after the onset of stroke; 10 patients with high DWI signal on the third examination had a fourth examination 12-28 months after the stroke. MRI was performed at 1.5 T, using echo-planar DWI with 7 b-values from 0 to 1200 x 10(6) s/m2 and conventional T2-weighted imaging. After 7-16 days 18 of 21 lesions gave high signal on DWI, and 12/16 measurable lesions had a decreased apparent diffusion coefficient (ADC). After 54-144 days ten lesions still gave high DWI signal and two still had an ADC below normal. On the fourth examination there was no remaining high DWI signal and all ADC were higher than normal.

Accuracy of segmented MR velocity mapping to measure small vessel pulsatile flow in a phantom simulating cardiac motion.

The purpose of this study was to investigate the accuracy of conventional, segmented, and echo-shared MR velocity mapping sequences to measure pulsatile flow in small moving vessels using a phantom with simulated cardiac motion. The phantom moved either cyclically in-plane, through-plane, in- and through-plane, or was stationary. The mean error in average flow was -2% +/- 3% (mean +/- SD) for all sequences under all conditions, with or without background correction, as long as the region of interest (ROI) size was equal to the vessel cross-sectional size. Overestimation of flow as a result of an oversized ROI was less than 20%, and independent of field of view (FOV) and matrix, as long as the offset in angle between the imaging plane and flow direction was less than 10 degrees. Segmented velocity mapping sequences are surprisingly accurate in measuring average flow and render flow profiles in small moving vessels despite the blurring in the images due to vessel motion. J. Magn. Reson. Imaging 2001;13:722-728.

Perfusion-related parameters in intravoxel incoherent motion MR imaging compared with CBV and CBF measured by dynamic susceptibility-contrast MR technique.

OBJECTIVE: Perfusion-related parameters obtained by intravoxel incoherent motion (IVIM) MR imaging (MRI) were compared with cerebral blood volume and flow (CBV and CBF), retrieved by dynamic susceptibility-contrast (DSC) MRI. MATERIAL AND METHODS: Twenty-eight volunteers (average age 68.5 years) were investigated. Spin-echo echo-planar imaging with IVIM-encoding gradients was employed (36 different b values, 0-1200 s/mm2). The perfusion fraction and the pseudo-diffusion coefficient were calculated for regions in thalamus gray matter and frontal white matter, using asymptotic and full fitting. In DSC-MRI, a Gd-DTPA-BMA contrast-agent bolus was monitored using simultaneous-dual FLASH. Deconvolution of the measured tissue concentration-versus-time curve with an arterial input function from the carotid artery was applied, and maps of CBV and CBF were calculated. RESULTS: The correlation between the perfusion fraction and CBV was r=0.56 (p<0.0000006) using asymptotic fitting, and r=0.35 (p<0.0004) when full fitting was applied. Average CBF was 41.5 ml/(min 100 g), to be compared with the IVIM-based value of 63.6 ml/(min 100 g), obtained from the median value of the pseudo-diffusion coefficient in combination with assumptions about capillary network structure. CONCLUSION: The IVIM concept provided results that agreed reasonably with conventional CBV and CBF. The non-linear fitting to noisy signal data was problematic, in accordance with previously presented simulations.

Contrast-enhanced thoracic 3D-MR angiography in infants and children.

PURPOSE: To optimise breath-hold contrast-enhanced MR angiography (MRA) in infants and children with suspected congenital heart or thoracic vessel malformation. MATERIAL AND METHODS: Thirty-nine children (median age 1 year) were examined, using five different ultrafast MRA sequences with a TR between 3.2 and 5.0 ms and the contrast agent meglumine gadoterate. A test injection was used to determine contrast travel time. Different parameters for contrast injection were evaluated. Signal-to-noise ratio (SNR) measurements were performed and image quality and injection timing were evaluated. RESULTS: MRA was successful in all patients and image quality was considered very good in 52%. Adequate SNR was achieved with no significant differences between the MR sequences. SNR decreased only 25-30% between subsequent scans. The mean contrast dose was 0.23 mmol/kg. The mean scan time was 12.5 +/- 3.8 s; the shorter scan times made dynamic examinations possible with high temporal resolution. Highest spatial resolution was obtained with TR 4.6/5.0 sequences. CONCLUSION: A contrast dose of 0.2 mmol/kg b.w. is recommended with an injection rate of 0.5 to 1.2 ml/s, depending on patient size and scan time. The scan delay time should equal the contrast travel time for optimal vessel enhancement. In the future, contrast-enhanced MRA may be a potential alternative to angiocardiography in infants and children.

Coronary sinus flow measurement by means of velocity-encoded cine MR imaging: validation by using flow probes in dogs.

PURPOSE: To validate coronary sinus flow measurements for quantification of global left ventricular (LV) perfusion by means of velocity-encoded cine (VEC) magnetic resonance (MR) imaging and flow probes. MATERIALS AND METHODS: Measurements of coronary sinus flow were performed in seven dogs by using VEC MR imaging at baseline, single coronary arterial stenosis, dipyridamole stress, and reactive hyperemia. These measurements were compared with flow probe measurements of coronary blood flow (CBF) in the left anterior descending coronary (LAD) and circumflex (CFX) arteries (CBF(LAD+CFX)) and coronary sinus. LV blood perfusion was calculated in milliliters per minute per gram from coronary sinus flow, and LV mass was obtained by using VEC and cine MR imaging. LV mass was validated at autopsy. RESULTS: CBF(LAD+CFX) and coronary sinus flow at VEC MR imaging showed close correlation (r = 0.98, P: <.001). The difference between CBF(LAD+CFX) and MR coronary sinus flow was 3.1 mL/min +/- 8.5 (SD). LV mass at cine MR imaging was not significantly different from that at autopsy (73.2 g +/- 12.8 vs 69. 4 g +/- 12.8). At baseline, myocardial perfusion was 0.40 mL/min/g +/- 0.09 at VEC MR imaging, and CBF(LAD+CFX) was 0.44 mL/min/g +/- 0. 08 (not significant). Reactive hyperemia resulted in 2.7- and 2. 3-fold increases in coronary sinus flow at VEC MR imaging and flow probe CBF(LAD+CFX), respectively. CONCLUSION: VEC MR imaging has the potential to measure coronary sinus flow during different physiologic conditions and can serve as a noninvasive modality to quantify global LV perfusion in patients.