Dissolved hyperpolarized xenon-129 MRI in human kidneys.

PURPOSE: To assess the feasibility of using dissolved hyperpolarized xenon-129 (129 Xe) MRI to study renal physiology in humans at 3 T. METHODS: Using a flexible transceiver RF coil, dynamic and spatially resolved 129 Xe spectroscopy was performed in the abdomen after inhalation of hyperpolarized 129 Xe gas with 3 healthy male volunteers. A transmit-only receive-only RF coil array was purpose-built to focus RF excitation and enhance sensitivity for dynamic imaging of 129 Xe uptake in the kidneys using spoiled gradient echo and balanced steady-state sequences. RESULTS: Using spatially resolved spectroscopy, different magnitudes of signal from 129 Xe dissolved in red blood cells and tissue/plasma could be identified in the kidneys and the aorta. The spectra from both kidneys showed peaks with similar amplitudes and chemical shift values. Imaging with the purpose-built coil array was shown to provide more than a 3-fold higher SNR in the kidneys when compared with surrounding tissues, while further physiological information from the dissolved 129 Xe in the lungs and in transit to the kidneys was provided with the transceiver coil. The signal of dissolved hyperpolarized 129 Xe could be imaged with both tested sequences for about 40 seconds after inhalation. CONCLUSION: The uptake of 129 Xe dissolved in the human kidneys was measured with spectroscopic and imaging experiments, demonstrating the potential of hyperpolarized 129 Xe MR as a novel, noninvasive technique to image human kidney tissue perfusion.

Exercise cardiac MRI unmasks right ventricular dysfunction in acute hypoxia and chronic pulmonary arterial hypertension.

Coupling of right ventricular (RV) contractility to afterload is maintained at rest in the early stages of pulmonary arterial hypertension (PAH), but exercise may unmask depleted contractile reserves. We assessed whether elevated afterload reduces RV contractile reserve despite compensated resting function using noninvasive exercise imaging. Fourteen patients with PAH (mean age: 39.1 yr, 10 women and 4 men) and 34 healthy control subjects (mean ageL 35.6 yr, 17 women and 17 men) completed real-time cardiac magnetic resonance imaging during submaximal exercise breathing room air. Control subjects were then also exercised during acute normobaric hypoxia (fraction of inspired O2: 12%). RV contractile reserve was assessed by the effect of exercise on ejection fraction. In control subjects, the increase in RV ejection fraction on exercise was less during hypoxia ( P = 0.017), but the response of left ventricular ejection fraction to exercise did not change. Patients with PAH had an impaired RV reserve, with half demonstrating a fall in RV ejection fraction on exercise despite comparable resting function to controls (PAH: rest 53.6 ± 4.3% vs. exercise 51.4 ± 10.7%; controls: rest 57.1 ± 5.2% vs. exercise 69.6 ± 6.1%, P < 0.0001). In control subjects, the increase in stroke volume index on exercise was driven by reduced RV end-systolic volume, whereas patients with PAH did not augment the stroke volume index, with increases in both end-diastolic and end-systolic volumes. From baseline hemodynamic and exercise capacity variables, only the minute ventilation-to-CO2 output ratio was an independent predictor of RV functional reserve ( P = 0.021). In conclusion, noninvasive cardiac imaging during exercise unmasks depleted RV contractile reserves in healthy adults under hypoxic conditions and patients with PAH under normoxic conditions despite preserved ejection fraction at rest. NEW & NOTEWORTHY Right ventricular (RV) reserve was assessed using real-time cardiac magnetic resonance imaging in patients with pulmonary arterial hypertension and in healthy control subjects under normobaric hypoxia, which has been previously associated with acute pulmonary hypertension. Hypoxia caused a mild reduction in RV reserve, whereas chronic pulmonary arterial hypertension was associated with a marked reduction in RV reserve.

Event-related dynamics of glutamate and BOLD effects measured using functional magnetic resonance spectroscopy (fMRS) at 3T in a repetition suppression paradigm.

Proton MR spectroscopy ((1)H-MRS) complements other brain research methods by providing measures of neurometabolites noninvasively in a localized brain area. Improvements in MR scanner technologies, and data acquisition and analysis methods should allow functional (1)H-MRS (fMRS) to measure neurometabolite concentration changes during task-induced brain activation. The aim of the current study was to further develop event-related fMRS at 3T to investigate glutamate dynamics in response to repetition suppression. A secondary aim was to investigate the relationship between blood-oxygen-level-dependent (BOLD) responses and glutamate dynamics in the same paradigm at the same time. A novel approach of interleaved water-suppressed (metabolite) and unsuppressed (water) fMRS was used to simultaneously detect the event-related dynamics of glutamate and BOLD signal to repetition suppression in the lateral occipital cortex of thirteen (N=13) volunteers. On average, (1)H-MRS-visible glutamate increased after novel visual stimuli presentations by 12% and decreased by 11-13% on repeated compared to novel presentations. The BOLD signal, as measured by water peak amplitude changes, showed significant difference between Task and Rest trials, and, on a GLM based analysis of the time series, demonstrated a significant difference between the novel and repeated trials, however appeared to be decoupled from the glutamate response as no correlation was found between the two. These results are the first demonstration that reductions in neuronal activity typical of repetition suppression effects are reflected by reduced glutamatergic and BOLD measures, that glutamate and BOLD responses may not be coupled as previously thought, and that these changes and relationships can be measured simultaneously using event-related fMRS at 3T.

Noninvasive in vivo magnetic resonance measures of glutathione synthesis in human and rat liver as an oxidative stress biomarker.

UNLABELLED: Oxidative stress (OS) plays a central role in the progression of liver disease and in damage to liver by toxic xenobiotics. We have developed methods for noninvasive assessment of hepatic OS defenses by measuring flux through the glutathione (GSH) synthesis pathway. (13) C-labeled GSH is endogenously produced and detected by in vivo magnetic resonance after administration of [2-(13) C]-glycine. We report on a successful first-ever human demonstration of this approach as well as preclinical studies demonstrating perturbed GSH metabolism in models of acute and chronic OS. Human studies employed oral administration of [2-(13) C]-glycine and (13) C spectroscopy on a 3T clinical magnetic resonance (MR) imaging scanner and demonstrated detection and quantification of endogenously produced (13) C-GSH after labeled glycine ingestion. Plasma analysis demonstrated that glycine (13) C fractional enrichment achieved steady state during the 6-hour ingestion period. Mean rate of synthesis of hepatic (13) C-labeled GSH was 0.32 ± 0.18 mmole/kg/hour. Preclinical models of acute OS and nonalcoholic steatohepatitis (NASH) comprised CCl4 -treated and high-fat, high-carbohydrate diet-fed Sprague-Dawley rats, respectively, using intravenous administration of [2-(13) C]-glycine and observation of (13) C-label metabolism on a 7T preclinical MR system. Preclinical studies demonstrated a 54% elevation of GSH content and a 31% increase in flux through the GSH synthesis pathway at 12 hours after acute insult caused by CCl4 administration, as well as a 23% decrease in GSH content and evidence of early steatohepatitis in the model of NASH. CONCLUSION: Our data demonstrate in vivo (13) C-labeling and detection of GSH as a biomarker of tissue OS defenses, detecting chronic and acute OS insults. The methods are applicable to clinical research studies of hepatic OS in disease states over time as well as monitoring effects of therapeutic interventions.

Sodium ((23)Na) ultra-short echo time imaging in the human brain using a 3D-Cones trajectory.

OBJECT: Sodium magnetic resonance imaging ((23)Na-MRI) of the brain has shown changes in (23)Na signal as a hallmark of various neurological diseases such as stroke, Alzheimer's disease, Multiple Sclerosis and Huntington's disease. To improve scan times and image quality, we have implemented the 3D-Cones (CN) sequence for in vivo (23)Na brain MRI. MATERIALS AND METHODS: Using signal-to-noise (SNR) as a measurement of sequence performance, CN is compared against more established 3D-radial k-space sampling schemes featuring cylindrical stack-of-stars (SOS) and 3D-spokes kooshball (KB) trajectories, on five healthy volunteers in a clinical setting. Resolution was evaluated by simulating the point-spread-functions (PSFs) and experimental measures on a phantom. RESULTS: All sequences were shown to have a similar SNR arbitrary units (AU) of 6-6.5 in brain white matter, 7-9 in gray matter and 17-18 AU in cerebrospinal fluid. SNR between white and gray matter were significantly different for KB and CN (p = 0.046 and <0.001 respectively), but not for SOS (p = 0.1). Group mean standard deviations were significantly smaller for CN (p = 0.016). Theoretical full-width at half-maximum linewidth of the PSF for CN is broadened by only 0.1, compared to 0.3 and 0.8 pixels for SOS and KB respectively. Actual image resolution is estimated as 8, 9 and 6.3 mm for SOS, KB and CN respectively. CONCLUSION: The CN sequence provides stronger tissue contrast than both SOS and KB, with more reproducible SNR measurements compared to KB. For CN, a higher true resolution in the same amount of time with no significant trade-off in SNR is achieved. CN is therefore more suitable for (23)Na-MRI in the brain.

Simultaneous imaging of lung structure and function with triple-nuclear hybrid MR imaging.

PURPOSE: To re-engineer a standard clinical magnetic resonance (MR) imaging system to enable the acquisition, in the same breath hold, of lung images from two hyperpolarized gases (helium 3 [(3)He] and xenon 129 [(129)Xe]) with simultaneous registered anatomic proton (hydrogen 1 [(1)H]) MR images of lung structure. MATERIALS AND METHODS: Studies with (3)He and (129)Xe were performed with National Research Ethics Committee approval, with informed consent from the volunteer. (1)H-(3)He-(129)Xe MR imaging was achieved in the same breath by using mutually decoupled nested radiofrequency coil hardware capable of transmit and receive on each respective nucleus without power cross talk. MR pulse sequences were also developed for rapid switching between each nucleus. The system is demonstrated with triple-nuclear lung images in a healthy individual following inhalation of a mixture of (3)He and (129)Xe gases. RESULTS: Spatially and temporally registered images of all three nuclei were obtained with high signal to noise ratio and high spatial resolution in the same breath. CONCLUSION: The multinuclear technique is capable of providing registered lung images with mutually complementary functional and structural spatial information.

Quantification of venous vessel size in human brain in response to hypercapnia and hyperoxia using magnetic resonance imaging.

Hypercapnia and hyperoxia give rise to vasodilation and vasoconstriction, respectively. This study investigates the influence of hypercapnia and hyperoxia on venous vessel size in the human brain. Venous vessel radii were measured in response to hypercapnia and hyperoxia. The venous vessel radii were determined by calculation of the changes in R2 * and R2 that are induced by breathing 6% CO2 or pure oxygen. The experimental paradigm consisted of two 3-min intervals of inhaling 6% CO2 or 100% O2 interleaved with three 2-min intervals of breathing air. Hypercapnic and hyperoxic experiments were performed on eight subjects on a 3T scanner. Parametric maps of mean venous vessel radius were calculated from the changes in R2 * and R2 , which were measured by simultaneous acquisition of gradient-echo and spin-echo signals. The mean venous vessel radii in hypercapnia were 7.3±0.3 µm in gray matter and 6.6±0.5 µm in white matter. The corresponding vessel radii in hyperoxia were 5.6±0.2 µm in gray matter and 5.4±0.2 µm in white matter. These results show that the venous vessel radius was larger in hypercapnia than that in hyperoxia in both gray matter and white matter (P<0.005), which agrees with the hypothesis that hypercapnia causes vasodilation and hyperoxia induces vasoconstriction.

High-resolution imaging of magnetisation transfer and nuclear Overhauser effect in the human visual cortex at 7 T.

The aim of this study was to optimise a pulse sequence for high-resolution imaging sensitive to the effects of conventional macromolecular magnetisation transfer (MT(m)) and nuclear Overhauser enhancement (NOE), and to use it to investigate variations in these parameters across the cerebral cortex. A high-spatial-resolution magnetisation transfer-prepared turbo field echo (MT-TFE) sequence was designed to have high sensitivity to MT(m) and NOE effects, whilst being robust to B0 and B1 inhomogeneities, and producing a good point spread function across the cortex. This was achieved by optimising the saturation and imaging components of the sequence using simulations based on the Bloch equations, including exchange and an image simulator. This was used to study variations in these parameters across the cortex. Using the sequence designed to be sensitive to NOE and MT(m), a variation in signals corresponding to a variation in MT(m) and NOE across the cortex, consistent with a reduction in myelination from the white matter surface to the pial surface of the cortex, was observed. In regions in which the stria was visible on T2*-weighted images, it could also be detected in signals sensitive to MT(m) and NOE. There was greater variation in signals sensitive to NOE, suggesting that the NOE signal is more sensitive to myelination. A sequence has been designed to image variations in MT(m) and NOE at high spatial resolution and has been used to investigate variations in contrast in these parameters across the cortex.

Magnetic resonance imaging of the mean venous vessel size in the human brain using transient hyperoxia.

Vessel size imaging is an emerging magnetic resonance imaging (MRI) technique which has been demonstrated to provide clinically relevant information about microvascular morphology. While previous studies of vessel size in humans relied on MRI contrast agents or hypercapnia-induced changes in blood oxygenation, the technique described here uses transient hyperoxia to alter the venous blood oxygenation. The experimental paradigm consisted of two 3-minute intervals of breathing 100% O(2) interleaved with three 2-minute intervals of breathing room air. Parametric maps of the mean venous vessel radius were calculated from changes in the blood oxygenation level dependent (BOLD) contrast which were measured using a combined spin-echo (SE) and gradient echo (GE) echo-planar imaging (EPI) sequence. The corresponding mean values in grey and white matter were r=6.5±0.3 µm and r=6.2±0.3 µm (n=6). While the hypercapnia technique requires a specialised gas mixture containing a low concentration of CO(2) (typically 5-6%), the hyperoxia technique presented here uses the inhalation of medical oxygen (100% O(2)) which is routinely available in a clinical environment. Furthermore, 100% O(2) is generally better tolerated than low doses of CO(2) which makes this technique particularly suitable for applications in critically ill patients.

Parametric Assessment of the Effect of Cochlear Implant Positioning on Brain MRI Artefacts at 3 T.

BACKGROUND: Brain magnetic resonance imaging in patients with cochlear implants (CIs) is impacted by image artefacts. HYPOTHESIS: The optimal positioning of the CI to minimize artefacts is unknown. This study aimed to characterize the dependence of the extent and distribution of the artefact on CI positioning. METHODS: Three normally hearing individuals underwent magnetic resonance imaging using a standard T1-weighted 3D sequence. Scans were acquired with a non-functioning CI placed underneath a swimming cap at four plausible scalp positions on each side, and without the CI in situ. The artefact in each image was assessed quantitatively using voxel-based techniques. Two radiologists also independently rated the likely impact of the artefact on the detection of pathology for 20 neuroradiological locations. RESULTS: The procedure was well tolerated. The most postero-inferior CI positions resulted in the smallest apparent artefacts. Radiological evaluations suggested that artefacts would likely limit pathology detection in the ipsilateral temporal, parietal, and occipital lobes, regardless of CI location. Pathology detection in contralateral structures and anterior corpus callosum was rarely affected. Certain CI locations appeared to selectively spare ipsilateral structures, for example, postero-inferior CI locations selectively spared ipsilateral midbrain, deep grey matter, and frontal lobes. CONCLUSION: A CI placed under a swimming cap is a feasible tool for observing the effect of CI location on image usability within a single subject and potentially informing surgical planning. Regardless of CI placement, artefacts involving ipsilateral parietal, temporal, and occipital lobes severely limited diagnostic image utility. Between 35% and 70% of neuroradiological features were deemed unaffected by the implant.

Clinical Validation of a 3-Dimensional Ultrafast Cardiac Magnetic Resonance Protocol Including Single Breath-Hold 3-Dimensional Sequences.

OBJECTIVES: This study sought to clinically validate a novel 3-dimensional (3D) ultrafast cardiac magnetic resonance (CMR) protocol including cine (anatomy and function) and late gadolinium enhancement (LGE), each in a single breath-hold. BACKGROUND: CMR is the reference tool for cardiac imaging but is time-consuming. METHODS: A protocol comprising isotropic 3D cine (Enhanced sensitivity encoding [SENSE] by Static Outer volume Subtraction [ESSOS]) and isotropic 3D LGE sequences was compared with a standard cine+LGE protocol in a prospective study of 107 patients (age 58 ± 11 years; 24% female). Left ventricular (LV) mass, volumes, and LV and right ventricular (RV) ejection fraction (LVEF, RVEF) were assessed by 3D ESSOS and 2D cine CMR. LGE (% LV) was assessed using 3D and 2D sequences. RESULTS: Three-dimensional and LGE acquisitions lasted 24 and 22 s, respectively. Three-dimensional and LGE images were of good quality and allowed quantification in all cases. Mean LVEF by 3D and 2D CMR were 51 ± 12% and 52 ± 12%, respectively, with excellent intermethod agreement (intraclass correlation coefficient [ICC]: 0.96; 95% confidence interval [CI]: 0.94 to 0.97) and insignificant bias. Mean RVEF 3D and 2D CMR were 60.4 ± 5.4% and 59.7 ± 5.2%, respectively, with acceptable intermethod agreement (ICC: 0.73; 95% CI: 0.63 to 0.81) and insignificant bias. Both 2D and 3D LGE showed excellent agreement, and intraobserver and interobserver agreement were excellent for 3D LGE. CONCLUSIONS: ESSOS single breath-hold 3D CMR allows accurate assessment of heart anatomy and function. Combining ESSOS with 3D LGE allows complete cardiac examination in <1 min of acquisition time. This protocol expands the indication for CMR, reduces costs, and increases patient comfort.

A functional-magnetic-resonance-imaging investigation of cortical activation from moving vibrotactile stimuli on the fingertip.

Using a 100-element tactile stimulator on the fingertip during functional-magnetic-resonance imaging, brain areas were identified that were selectively activated by a moving vibrotactile stimulus (the sensation of a moving line being dragged over the fingertip). Activation patterns elicited by tactile motion, contrasted to an equivalent stationary stimulus, were compared in six human subjects with those generated by a moving visual stimulus, contrasted to an equivalent stationary stimulus. Results provide further evidence for a neuroanatomical convergence of tactile-motion processing and visual-motion processing in humans. The sites of this convergence are found to lie in the middle temporal complex (hMT+V5), an area with known specialization for visual-motion processing, and in the intraparietal area of the posterior parietal cortex. In an advance on previous studies, the present study includes separate delineation of activations for moving tactile stimuli and activations for moving visual stimuli. Results suggest that the two sets of activations are not entirely collocated. Compared to the visual-motion activations, the tactile-motion activations are found to lie nearer the midline of the brain and further superior.

Cadaveric and MRI study of the musculotendinous contributions to the capsule of the symphysis pubis.

OBJECTIVE: The purpose of this article is to define the relations of the symphysis pubis and capsular tissues to the adductor and rectus abdominis soft-tissue attachments on cadaver dissection and correlate with MRI of the anterior pelvis. SUBJECTS AND METHODS: Seventeen cadavers (8 males and 9 females; mean age, 80 years) were dissected bilaterally. Rectus abdominis and adductor muscles were traced to the pubis and further attachments to the pubic symphysis were defined. Ten asymptomatic (mean age, 17; age range, 16.5-29 years) male athletes underwent 1.5-T MRI of the anterior pelvis with two surface microcoils (each 42 mm in diameter). An axial T2-weighted turbo spin-echo (TSE) sequence (TR/TE, 2,609/106; voxel size, 0.4 mm) was obtained. Axial and sagittal 3D T1-weighted fast-field echo (FFE) sequences (25/4.9; voxel size, 0.3 mm) were obtained. Sequences were repeated incorporating fat suppression and i.v. gadolinium. The relation of the symphysis pubis, disk, and capsular tissues to the insertions of the rectus abdominis, adductor muscles, and gracilis were independently evaluated by two experienced radiologists blinded to all clinical details. RESULTS: In all 17 cadaver specimens, the adductor longus and rectus abdominis attached to the capsule and disk of the symphysis pubis, whereas the adductor brevis had an attachment to the capsule in seven specimens and the gracilis in one. All adductor tendons attached to the pubis. In all 10 athletes, the adductor longus and rectus abdominis bilaterally contributed to the capsular tissues and disk. This was only the case for the adductor brevis in four athletes. No other tendons involved the capsular tissues. CONCLUSION: Cadaver and MRI findings show an intimate relationship between the adductor longus; rectus abdominis; and symphyseal cartilage, disk, and capsular tissues.

Susceptibility effects in hyperpolarized (3)He lung MRI at 1.5T and 3T.

PURPOSE: To compare susceptibility effects in hyperpolarized (3)He lung MRI at the clinically relevant field strengths of 1.5T and 3T. MATERIALS AND METHODS: Susceptibility-related B(0) inhomogeneity was evaluated on a macroscopic scale by B(0) field mapping via phase difference. Subpixel susceptibility effects were quantified by mapping T2. Comparison was made between ventilation images obtained from the same volunteers at both field strengths. RESULTS: The B(0) maps at 3T show enhanced off-resonance effects close to the diaphragm and the ribs due to susceptibility differences. The average T2 from a voxel (20 x 4 x 4) mm(3) was determined as T2 = 27.8 msec +/- 1.2 msec at 1.5T compared to T2 = 14.4 msec +/- 2.6 msec at 3T. In ventilation images the most prominent effect is increased signal attenuation close to the intrapulmonary blood vessels at higher B(0). CONCLUSION: Image homogeneity and T2 are lower at 3T due to increased B(0) inhomogeneity as a consequence of susceptibility differences. These findings indicate that (3)He imaging at 3T has no obvious benefit over imaging at 1.5T, as signal-to-noise ratio (SNR) was comparable for both fields in this work.

Delayed hypothermia prevents decreases in N-acetylaspartate and reduced glutathione in the cerebral cortex of the neonatal pig following transient hypoxia-ischaemia.

The effects of normothermia and delayed hypothermia on the levels of N-acetylaspartate (NAA), reduced glutathione (GSH) and the activities of mitochondrial complex I, II-III, IV and citrate synthase were measured in brain homogenates obtained from anaesthetized neonatal pigs following transient in vivo hypoxia-ischaemia. In the normothermic animals there was a significant decrease in complex I activity and in the levels of GSH and NAA when compared to the controls. Delayed hypothermia preserved NAA and GSH at control levels and enhanced the rate of complex II-III activity. There was correlation (R = 0.79) between GSH and NAA levels when data from all three experimental groups were analyzed. Citrate synthase activity was not significantly different in the three groups, indicating maintenance of mitochondrial integrity. These data suggest that delayed hypothermia affords protection of integrated mitochondrial function in the neonatal brain following transient hypoxia-ischaemia.