Targeted magnetic resonance imaging (tMRI) of small changes in the T1 and spatial properties of normal or near normal appearing white and gray matter in disease of the brain using divided subtracted inversion recovery (dSIR) and divided reverse subtracted inversion recovery (drSIR) sequences.

This review describes targeted magnetic resonance imaging (tMRI) of small changes in the T1 and the spatial properties of normal or near normal appearing white or gray matter in disease of the brain. It employs divided subtracted inversion recovery (dSIR) and divided reverse subtracted inversion recovery (drSIR) sequences to increase the contrast produced by small changes in T1 by up to 15 times compared to conventional T1-weighted inversion recovery (IR) sequences such as magnetization prepared-rapid acquisition gradient echo (MP-RAGE). This increase in contrast can be used to reveal disease with only small changes in T1 in normal appearing white or gray matter that is not apparent on conventional MP-RAGE, T2-weighted spin echo (T2-wSE) and/or fluid attenuated inversion recovery (T2-FLAIR) images. The small changes in T1 or T2 in disease are insufficient to produce useful contrast with conventional sequences. To produce high contrast dSIR and drSIR sequences typically need to be targeted for the nulling TI of normal white or gray matter, as well as for the sign and size of the change in T1 in these tissues in disease. The dSIR sequence also shows high signal boundaries between white and gray matter. dSIR and drSIR are essentially T1 maps. There is a nearly linear relationship between signal and T1 in the middle domain (mD) of the two sequences which includes T1s between the nulling T1s of the two acquired IR sequences. The drSIR sequence is also very sensitive to reductions in T1 produced by Gadolinium based contrast agents (GBCAs), and when used with rigid body registration to align three-dimensional (3D) isotropic pre and post GBCA images may be of considerable value in showing subtle GBCA enhancement. In serial MRI studies performed at different times, the high signal boundaries generated by dSIR and drSIR sequences can be used with rigid body registration of 3D isotropic images to demonstrate contrast arising from small changes in T1 (without or with GBCA enhancement) as well as small changes in the spatial properties of normal tissues and lesions, such as their site, shape, size and surface. Applications of the sequences in cases of multiple sclerosis (MS) and methamphetamine dependency are illustrated. Using targeted narrow mD dSIR sequences, widespread abnormalities were seen in areas of normal appearing white matter shown with conventional T2-wSE and T2-FLAIR sequences. Understanding of the features of dSIR and drSIR images is facilitated by the use of their T1-bipolar filters; to explain their targeting, signal, contrast, boundaries, T1 mapping and GBCA enhancement. Targeted MRI (tMRI) using dSIR and drSIR sequences may substantially improve clinical MRI of the brain by providing unequivocal demonstration of abnormalities that are not seen with conventional sequences.

Development of a Personalised Device for Systemic Magnetic Drug Targeting to Brain Tumours.

Delivering therapies to deeply seated brain tumours (BT) is a major clinical challenge. Magnetic drug targeting (MDT) could overcome this by rapidly transporting magnetised drugs directly into BT. We have developed a magnetic device for application in murine BT models using an array of neodymium magnets with a combined strength of 0.7T. In a closed fluidic system, the magnetic device trapped magnetic nanoparticles (MNP) up to distances of 0.8cm. In mice, the magnetic device guided intravenously administered MNP (<50nm) from the circulation into the brain where they localised within mouse BT. Furthermore, MDT of magnetised Temozolomide (TMZmag+) significantly reduced tumour growth and extended mouse survival to 48 days compared to the other treatment groups. Using the same principles, we built a proof of principle scalable magnetic device for human use with a strength of 1.1T. This magnetic device demonstrated trapping of MNP undergoing flow at distances up to 5cm. MDT using our magnetic device provides an opportunity for targeted delivery of magnetised drugs to human BT.

Kinetic modelling of dissolution dynamic nuclear polarisation 13 C magnetic resonance spectroscopy data for analysis of pyruvate delivery and fate in tumours.

Dissolution dynamic nuclear polarisation (dDNP) of 13 C-labelled pyruvate in magnetic resonance spectroscopy/imaging (MRS/MRSI) has the potential for monitoring tumour progression and treatment response. Pyruvate delivery, its metabolism to lactate and efflux were investigated in rat P22 sarcomas following simultaneous intravenous administration of hyperpolarised 13 C-labelled pyruvate (13 C1 -pyruvate) and urea (13 C-urea), a nonmetabolised marker. A general mathematical model of pyruvate-lactate exchange, incorporating an arterial input function (AIF), enabled the losses of pyruvate and lactate from tumour to be estimated, in addition to the clearance rate of pyruvate signal from blood into tumour, Kip , and the forward and reverse fractional rate constants for pyruvate-lactate signal exchange, kpl and klp . An analogous model was developed for urea, enabling estimation of urea tumour losses and the blood clearance parameter, Kiu . A spectral fitting procedure to blood time-course data proved superior to assuming a gamma-variate form for the AIFs. Mean arterial blood pressure marginally correlated with clearance rates. Kiu equalled Kip , indicating equivalent permeability of the tumour vasculature to urea and pyruvate. Fractional loss rate constants due to effluxes of pyruvate, lactate and urea from tumour tissue into blood (kpo , klo and kuo , respectively) indicated that T1 s and the average flip angle, θ, obtained from arterial blood were poor surrogates for these parameters in tumour tissue. A precursor-product model, using the tumour pyruvate signal time-course as the input for the corresponding lactate signal time-course, was modified to account for the observed delay between them. The corresponding fractional rate constant, kavail , most likely reflected heterogeneous tumour microcirculation. Loss parameters, estimated from this model with different TRs, provided a lower limit on the estimates of tumour T1 for lactate and urea. The results do not support use of hyperpolarised urea for providing information on the tumour microcirculation over and above what can be obtained from pyruvate alone. The results also highlight the need for rigorous processes controlling signal quantitation, if absolute estimations of biological parameters are required.

Evidence for Rapid Oxidative Phosphorylation and Lactate Fermentation in Motile Human Sperm by Hyperpolarized 13C Magnetic Resonance Spectroscopy.

Poor sperm motility is a common cause of male infertility for which there are no empirical therapies. Sperm motility is powered by adenosine triphosphate but the relative importance of lactate fermentation and Oxidative Phosphorylation (OxPhos) is debated. To study the relationship between energy metabolism and sperm motility we used dissolution Dynamic Nuclear Polarization (dDNP) for the first time to show the rapid conversion of 13C1-pyruvate to lactate and bicarbonate, indicating active glycolytic and OxPhos metabolism in sperm. The magnitude of both lactate and bicarbonate signals were positively correlated with the concentration of progressively motile sperm. After controlling for sperm concentration, increased progressive sperm motility generated more pyruvate conversion to lactate and bicarbonate. The technique of dDNP allows 'snapshots' of sperm metabolism to be tracked over the different stages of their life. This may provide help to uncover the causes of poor sperm motility and suggest new approaches for novel treatments or therapies.

Direct arterial injection of hyperpolarized 13 C-labeled substrates into rat tumors for rapid MR detection of metabolism with minimal substrate dilution.

PURPOSE: A rat model was developed to enable direct administration of hyperpolarized 13 C-labeled molecules into a tumor-supplying artery for magnetic resonance spectroscopy (MRS) studies of tumor metabolism. METHODS: Rat P22 sarcomas were implanted into the right inguinal fat pad of BDIX rats such that the developing tumors received their principle blood supply directly from the right superior epigastric artery. Hyperpolarized 13 C-molecules were either infused directly to the tumor through the epigastric artery or systemically through the contralateral femoral vein. Spectroscopic data were obtained on a 7 Tesla preclinical scanner. RESULTS: Intra-arterial infusion of hyperpolarized 13 C-pyruvate increased the pyruvate tumor signal by a factor of 4.6, compared with intravenous infusion, despite an approximately 7 times smaller total dose to the rat. Hyperpolarized glucose signal was detected at near-physiological systemic blood concentration. Pyruvate to lactate but not glucose to lactate metabolism was detected in the tumor. Hyperpolarized 13 C-labeled combretastatin A1 diphosphate, a tumor vascular disrupting agent, showed an in vivo signal in the tumor. CONCLUSIONS: The model maximizes tumor substrate/drug delivery and minimizes T1 relaxation signal losses in addition to systemic toxicity. Therefore, it permits metabolic studies of hyperpolarized substrates with relatively short T1 and opens up the possibility for preclinical studies of hyperpolarized drug molecules. Magn Reson Med 78:2116-2126, 2017. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Measurement of the acute metabolic response to hypoxia in rat tumours in vivo using magnetic resonance spectroscopy and hyperpolarised pyruvate.

PURPOSE: To estimate the rate constant for pyruvate to lactate conversion in tumours in response to a hypoxic challenge, using hyperpolarised (13)C1-pyruvate and magnetic resonance spectroscopy. METHODS AND MATERIALS: Hypoxic inspired gas was used to manipulate rat P22 fibrosarcoma oxygen tension (pO2), confirmed by luminescence decay of oxygen-sensitive probes. Hyperpolarised (13)C1-pyruvate was injected into the femoral vein of anaesthetised rats and slice-localised (13)C magnetic resonance (MR) spectra acquired. Spectral integral versus time curves for pyruvate and lactate were fitted to a precursor-product model to estimate the rate constant for tumour conversion of pyruvate to lactate (kpl). Mean arterial blood pressure (MABP) and oxygen tension (ArtpO2) were monitored. Pyruvate and lactate concentrations were measured in freeze-clamped tumours. RESULTS: MABP, ArtpO2 and tumour pO2 decreased significantly during hypoxia. kpl increased significantly (p<0.01) from 0.029±0.002s(-1) to 0.049±0.006s(-1) (mean±SEM) when animals breathing air were switched to hypoxic conditions, whereas pyruvate and lactate concentrations were minimally affected by hypoxia. Both ArtpO2 and MABP influenced the estimate of kpl, with a strong negative correlation between kpl and the product of ArtpO2 and MABP under hypoxia. CONCLUSION: The rate constant for pyruvate to lactate conversion, kpl, responds significantly to a rapid reduction in tumour oxygenation.

NMR-based evaluation of the metabolic profile and response to dichloroacetate of human prostate cancer cells.

The aim of this study was to evaluate the metabolic profile of human prostate cancer cells that have different metastatic potential and to determine their response to dichloroacetate (DCA) using NMR technology. Two isogenic human prostate cancer cell lines, differing in their metastatic potential [LNCaP (poorly metastatic) and LNCaP-LN3 (highly metastatic)], were studied. Metabolite ratios from NMR spectral integrals acquired at a field strength of 9.4 T using a 5-mm broadband probe with an NMR-compatible bioreactor were compared in the presence and absence of the pyruvate dehydrogenase kinase inhibitor DCA. Lactate dehydrogenase (LDH) isoenzymes were assessed by zymography. Following the treatment of cells with 50 mm DCA, there was a significant reduction in the lactate/choline, lactate/creatine, lactate/alanine and the combined lactate/(choline + creatine + alanine) ratios in LNCaP-LN3 cells relative to LNCaP cells. No significant changes in metabolite ratios were found in LNCaP cells following DCA treatment. As expected, LDH zymography assays showed an absence of the LDH-B subunit in LNCaP-LN3 cells, whereas both LDH-A and LDH-B subunits were present in LNCaP cells. DCA was shown to significantly modify the metabolite ratios in highly metastatic LNCaP-LN3 cells, but not in poorly metastatic LNCaP cells. This effect was probably related to the absence of the LDH-B subunit in LNCaP-LN3 cells, and could have a bearing on cancer treatment with DCA and related compounds.

MALDI-MSI and label-free LC-ESI-MS/MS shotgun proteomics to investigate protein induction in a murine fibrosarcoma model following treatment with a vascular disrupting agent.

Tumour vasculature is notoriously sinusoidal and leaky, and is hence susceptible to vascular disruption. Microtubule destabilising drugs such as the combretastatins form the largest group of tumour vascular disrupting agents and cause selective shutdown of tumour blood flow within minutes to hours, leading to secondary tumour cell death. Targeting the tumour vasculature is a proven anticancer strategy but early treatment response biomarkers are required for personalising treatment planning. Protein induction following treatment with combretastatin A4-phosphate was examined in a mouse fibrosarcoma model (fs188), where tumour cells express only the matrix-bound isoform of vascular endothelial growth factor A (VEGF188). These tumours are relatively resistant to vascular disruption by combretastatin A4-phosphate and hence a study of protein induction following treatment could yield insights into resistance mechanisms. The distribution of a number of proteins induced following treatment were visualised by MALDI-mass spectrometry imaging. Responses identified were validated by LC-ESI-MS/MS and immunohistochemical staining. Significant changes in proteins connected with necrosis, cell structure, cell survival and stress-induced molecular chaperones were identified. Protein-protein interactions were identified using STRING 9.0 proteomic network software. These relationship pathways provided an insight into the activity of the active tumour milieu and a means of linking the identified proteins to their functional partners.

A system for accurate and automated injection of hyperpolarized substrate with minimal dead time and scalable volumes over a large range.

Over recent years hyperpolarization by dissolution dynamic nuclear polarization has become an established technique for studying metabolism in vivo in animal models. Temporal signal plots obtained from the injected metabolite and daughter products, e.g. pyruvate and lactate, can be fitted to compartmental models to estimate kinetic rate constants. Modeling and physiological parameter estimation can be made more robust by consistent and reproducible injections through automation. An injection system previously developed by us was limited in the injectable volume to between 0.6 and 2.4ml and injection was delayed due to a required syringe filling step. An improved MR-compatible injector system has been developed that measures the pH of injected substrate, uses flow control to reduce dead volume within the injection cannula and can be operated over a larger volume range. The delay time to injection has been minimized by removing the syringe filling step by use of a peristaltic pump. For 100µl to 10.000ml, the volume range typically used for mice to rabbits, the average delivered volume was 97.8% of the demand volume. The standard deviation of delivered volumes was 7µl for 100µl and 20µl for 10.000ml demand volumes (mean S.D. was 9 ul in this range). In three repeat injections through a fixed 0.96mm O.D. tube the coefficient of variation for the area under the curve was 2%. For in vivo injections of hyperpolarized pyruvate in tumor-bearing rats, signal was first detected in the input femoral vein cannula at 3-4s post-injection trigger signal and at 9-12s in tumor tissue. The pH of the injected pyruvate was 7.1±0.3 (mean±S.D., n=10). For small injection volumes, e.g. less than 100µl, the internal diameter of the tubing contained within the peristaltic pump could be reduced to improve accuracy. Larger injection volumes are limited only by the size of the receiving vessel connected to the pump.

Metal-on-metal hip prostheses and systemic health: a cross-sectional association study 8 years after implantation.

There is public concern over the long term systemic health effects of metal released from hip replacement prostheses that use large-diameter metal-on-metal bearings. However, to date there has been no systematic study to determine which organs may be at risk, or the magnitude of any effect. We undertook a detailed cross-sectional health screen at a mean of 8 years after surgery in 35 asymptomatic patients who had previously received a metal-on-metal hip resurfacing (MoMHR) versus 35 individually age and sex matched asymptomatic patients who had received a conventional hip replacement. Total body bone mineral density was 5% higher (mean difference 0.05 g/cm², P = 0.02) and bone turnover was 14% lower (TRAP 5b, mean difference -0.56IU/L, P = 0.006; osteocalcin, mean difference -3.08 ng/mL, P = 0.03) in the hip resurfacing versus conventional hip replacement group. Cardiac ejection fraction was 7% lower (mean absolute difference -5%, P = 0.04) and left ventricular end-diastolic diameter was 6% larger (mean difference 2.7 mm, P = 0.007) in the hip resurfacing group versus those patients who received a conventional hip replacement. The urinary fractional excretion of metal was low (cobalt 5%, chromium 1.5%) in patients with MoMHR, but creatinine clearance was normal. Diuretic prescription was associated with a 40% increase in the fractional excretion of chromium (mean difference 0.5%, P = 0.03). There was no evidence of difference in neuropsychological, renal tubular, hepatic or endocrine function between groups (P>0.05). Our findings of differences in bone and cardiac function between patient groups suggest that chronic exposure to low elevated metal concentrations in patients with well-functioning MoMHR prostheses may have systemic effects. Long-term epidemiological studies in patients with well-functioning metal on metal hip prostheses should include musculoskeletal and cardiac endpoints to quantitate the risk of clinical disease.

MRI assessment of basal ganglia iron deposition in Parkinson's disease.

PURPOSE: To estimate the levels of basal ganglia iron levels in Parkinson's disease (PD) using the PRIME MR sequence at 3.0 Tesla, in relation to patients' motor symptom severity. MATERIALS AND METHODS: Seventy patients with PD and 10 healthy controls underwent assessment of movement and MR imaging. Mean R2' relaxation rates were recorded in the substantia nigra, frontal white matter and in the rostral, mid, and caudal putamen. RESULTS: R2' relaxation rates were significantly higher in patients with PD than in healthy controls. R2' in the most affected substantia nigra correlated with PD patients' motor symptom severity, but not with disease duration. Neuroradiological observation revealed a rostral to caudal "gradient" of putaminal hypointensity. This was substantiated by the finding that the mid and caudal putamen showed significantly higher R2' relaxation rates, consistent with higher iron levels in PD relative to the healthy controls. CONCLUSION: MRI at 3.0 Tesla suggests that substantia nigra iron levels are increased and linked to the severity of motor symptoms experienced in PD. Findings consistent with increased iron levels in the PD putamen are shown, in a region-specific rostral to caudal gradient.

Quantitative analysis of regional airways obstruction using dynamic hyperpolarized 3He MRI-preliminary results in children with cystic fibrosis.

PURPOSE: To investigate regional airways obstruction in patients with cystic fibrosis (CF) with quantitative analysis of dynamic hyperpolarized (HP) (3)He MRI. MATERIALS AND METHODS: Dynamic radial projection MRI of HP (3)He gas was used to study respiratory dynamics in a group of eight children with CF. Signal kinetics in a total of seven regions of interest (ROIs; three in each lung, and one in the trachea) were compared with the results of spirometric pulmonary function tests (PFTs). The tracheal signal intensity was used as a form of "input function" to normalize for input flow effects. RESULTS: A pattern of low flow rate in the upper lobes was observed. When the flow measurements from the peripheral ROIs were averaged to obtain an index of flow in the peripheral lung, a good correlation was found (P = 3.74 x 10(-5)) with the forced expired volume in one second (FEV1). CONCLUSION: These results suggest that a quantitative measurement of localized airways obstruction in the early stages of CF may be obtained from dynamic (3)He MRI by using the slope of the signal rise as a measure of air flow into the peripheral lung. This study also demonstrates that children can cooperate well with the (3)He MRI technique.

Postmortem MR imaging of the fetus: an adjunct or a replacement for conventional autopsy?

Fetal and perinatal autopsy provides essential diagnostic information not only for parents but also for medical audit and clinical trials. The autopsy rate is decreasing throughout the world for numerous reasons. Medical imaging has always been part of the autopsy process, but in the last decade there has been increased interest in imaging as additional to or a replacement for autopsy. This is especially so with the wider availability of magnetic resonance (MR) scanners that are able to provide detailed anatomy of all body structures as well as having the potential to provide information about histopathological patterns of injury. Postmortem MR imaging (MRI) provides similar information to autopsy for gross pathology of most organ systems. It often provides more information in cases of central nervous system abnormalities, but is less accurate for cardiac abnormalities. Targeted, image-guided biopsy may allow histological diagnosis following postmortem MRI.

Emphysematous changes and normal variation in smokers and COPD patients using diffusion 3He MRI.

INTRODUCTION: This study aims to quantify global and regional changes of diffusive motion of 3He gas within the lung, as determined by hyperpolarized 3He MR apparent diffusion coefficient (ADC) measurement, in non-smokers, smokers and chronic obstructive pulmonary disease (COPD) patients. METHODS: Age-matched groups of six healthy non-smokers, five healthy smokers and five patients with COPD. The experiments were performed with approval from the local Research Ethics Committee. Diffusion imaging was performed following hyperpolarized 3He gas inhalation, producing ADC maps. Mean and standard deviation of the ADCs were used to compare the subject groups and assess regional variations within individuals. RESULTS: The intra-individual standard deviation of ADC in the healthy smokers was significantly larger than that of the non-smoking group (P < 0.02). Compared to the non-smoking group, COPD patients had significantly higher mean and standard deviation of ADC (P < 0.01). The mean ADC in the anterior half of the chest was systematically higher than in the posterior half in the healthy non-smoking subject group. DISCUSSION: This study suggests that there are regional trends in the ADC values of healthy volunteers that may have implications for the clinical interpretation of ADC values. Less homogeneous ADC values have been detected in asymptomatic smokers, indicative of damage to the distal air spaces.

Combined helium-3/proton magnetic resonance imaging measurement of ventilated lung volumes in smokers compared to never-smokers.

PURPOSE: To use a combination of helium-3 (3-He) magnetic resonance imaging (MRI) and proton single-shot fast spin echo (SSFSE) to compare ventilated lung volumes in groups of "healthy" smokers, smokers diagnosed with moderate chronic obstructive pulmonary disease (COPD), and never-smokers. MATERIALS AND METHODS: All study participants were assessed with spirometry prior to imaging. 3-He images were collected during an arrested breath hold, after inhaling a mixture of 200 mL of hyperpolarized 3-He/800 mL of N2. Proton SSFSE images were acquired after inhaling 1 liter of room air. The ventilated volume for each study participant was calculated from the 3-He images, and a ratio was calculated to give a percentage ventilated lung volume. RESULTS: Never-smokers exhibited a 90% mean ventilated volume. The mean ventilated lung volumes for healthy smokers and smokers diagnosed with COPD were 75.2% and 67.6%, respectively. No correlation with spirometry was demonstrated for either of the smoking groups. CONCLUSION: Combined 3-He/Proton SSFSE MRI of the lungs is a noninvasive method, using nonionizing radiation, which demonstrates ventilated airspaces and enables the calculation of ventilated lung volumes. This method appears to be sensitive to early obstructive changes in the lungs of smokers.

MRI of helium-3 gas in healthy lungs: posture related variations of alveolar size.

PURPOSE: To probe the variation of alveolar size in healthy lung tissue as a function of posture using diffusion-weighted helium-3 hyperpolarized gas imaging. MATERIALS AND METHODS: Measurements of the helium-3 apparent diffusion coefficient (ADC) were made on six healthy subjects. These were used to show the variation of alveolar size between the lowermost dependent regions of the lung compared to the uppermost regions of the lung in four postures: supine, prone, left-lateral decubitus, and right-lateral decubitus. RESULTS: The distribution of acinar size in the lungs was found to be heterogeneous, and influenced by lung orientation. In nearly all postures, the ADC was significantly higher in the non-dependent uppermost regions of the lung compared to the dependent lowermost regions of the lung; the greatest variation was found in the left-lateral decubitus position. The difference in ADC between uppermost and lowermost regions was on average 0.012 cm(2)second(-1), which represents 20% of the average ADC value for the whole lung. A systematic decrease in ADC from the apex of the lung to the base was also found, which corresponds to an inherent gradient in alveolar size. CONCLUSION: The posture dependent variations in ADC were attributed to compression of the parenchyma under its own weight and the mass of the heart.

Investigating 3He diffusion NMR in the lungs using finite difference simulations and in vivo PGSE experiments.

Finite difference simulations have been used to model (3)He gas diffusion in simulated lung tissue. The technique has the advantage that a wide range of structural models and diffusion-sensitizing gradient waveforms can be investigated, for which analytical methods would otherwise be virtually impossible. Results from simulations and in vivo pulsed-gradient-spin-echo (PGSE) experiments show that the apparent diffusion coefficient (ADC) is a function of diffusion time and gradient strength, and suggests diffusion is locally anisotropic. The simulations have been compared to recent work on an analytical model that characterizes lung tissue as a series of independent cylinders. The results presented may have clinical implications for (3)He ADC measurements in assessing lung diseases such as chronic-obstructive-pulmonary-disease.

Assessment and compensation of susceptibility artifacts in gradient echo MRI of hyperpolarized 3He gas.

The effects of macroscopic background field gradients upon 2D gradient echo images of inhaled (3)He in the human lung were investigated at 1.5 T. Effective compensation of in-slice signal loss in (3)He gradient echo images was then demonstrated using a multiple acquisition interleaved single gradient echo sequence. This method restores signal dephasing through a combination of separate images acquired with different slice refocusing gradients. In vivo imaging of volunteers with the sequence shows substantial restoration of signal at the lung periphery and close to blood vessels. The technique presented may be useful when using (3)He MRI for volumetric measurements of lung ventilation and in studies using (3)He combined with intravenous contrast as a means of assessing lung ventilation/perfusion (V/Q).

Dynamic radial projection MRI of inhaled hyperpolarized 3He gas.

A radial projection sliding-window sequence has been developed for imaging the rapid flow of (3)He gas in human lungs. The short echo time (TE) of the radial sequence lends itself to fast repetition times, and thus allows a rapid update in the image when it is reconstructed with a sliding window. Oversampling in the radial direction combined with angular undersampling can further reduce the time needed to acquire a complete image data set, without significantly compromising spatial resolution. Controlled flow phantom experiments using hyperpolarized (3)He gas exemplify the temporal resolution of the method. In vivo studies on three healthy volunteers, one patient with chronic obstructive pulmonary disease (COPD), and one patient with hemiparalysis of the right diaphragm demonstrate that it is possible to accurately resolve the passage of gas down the trachea and bronchi and into the peripheral lung.