Simultaneous quantification of hyperpolarized xenon-129 ventilation and gas exchange with multi-breath xenon-polarization transfer contrast (XTC) MRI.

PURPOSE: To demonstrate the feasibility of a multi-breath xenon-polarization transfer contrast (XTC) MR imaging approach for simultaneously evaluating regional ventilation and gas exchange parameters. METHODS: Imaging was performed in five healthy volunteers and six chronic obstructive pulmonary disease (COPD) patients. The multi-breath XTC protocol consisted of three repeated schemes of six wash-in breaths of a xenon mixture and four normoxic wash-out breaths, with and without selective saturation of either the tissue membrane or red blood cell (RBC) resonances. Acquisitions were performed at end-exhalation while subjects maintained tidal breathing throughout the session. The no-saturation, membrane-saturation, and RBC-saturation images were fit to a per-breath gas replacement model for extracting voxelwise tidal volume (TV), functional residual capacity (FRC), and fractional ventilation (FV), as well as tissue- and RBC-gas exchange (fMem and fRBC , respectively). The sensitivity of the derived model was also evaluated via simulations. RESULTS: With the exception of FRC, whole-lung averages for all metrics were decreased in the COPD subjects compared to the healthy cohort, significantly so for FV, fRBC , and fMem . Heterogeneity was higher overall in the COPD subjects, particularly for fRBC , fMem , and fRBC:Mem . The anterior-to-posterior gradient associated with the gravity-dependence of lung function in supine imaging was also evident for FV, fRBC , and fMem values in the healthy subjects, but noticeably absent in the COPD cohort. CONCLUSION: Multi-breath XTC imaging generated high-resolution, co-registered maps of ventilation and gas exchange parameters acquired during tidal breathing and with low per-breath xenon doses. Clear differences between healthy and COPD subjects were apparent and consistent with spirometry.

Investigating the impact of RF saturation-pulse parameters on compartment-selective gas-phase depolarization with xenon polarization transfer contrast MRI.

PURPOSE: To demonstrate the utility of continuous-wave (CW) saturation pulses in xenon-polarization transfer contrast (XTC) MRI and MRS, to investigate the selectivity of CW pulses applied to dissolved-phase resonances, and to develop a correction method for measurement biases from saturation of the nontargeted dissolved-phase compartment. METHODS: Studies were performed in six healthy Sprague-Dawley rats over a series of end-exhale breath holds. Discrete saturation schemes included a series of 30 Gaussian pulses (8 ms FWHM), spaced 25 ms apart; CW saturation schemes included single block pulses, with variable flip angle and duration. In XTC imaging, saturation pulses were applied on both dissolved-phase resonance frequencies and off-resonance, to correct for other sources of signal loss and compromised selectivity. In spectroscopy experiments, saturation pulses were applied at a set of 19 frequencies spread out between 185 and 200 ppm to map out modified z-spectra. RESULTS: Both modified z-spectra and imaging results showed that CW RF pulses offer sufficient depolarization and improved selectivity for generating contrast between presaturation and postsaturation acquisitions. A comparison of results obtained using a variety of saturation parameters confirms that saturation pulses applied at higher powers exhibit increased cross-contamination between dissolved-phase resonances. CONCLUSION: Using CW RF saturation pulses in XTC contrast preparation, with the proposed correction method, offers a potentially more selective alternative to traditional discrete saturation. The suppression of the red blood cell contribution to the gas-phase depolarization opens the door to a novel way of quantifying exchange time between alveolar volume and hemoglobin.

Imatinib alleviates lung injury and prolongs survival in ventilated rats.

Imatinib, a tyrosine kinase inhibitor, attenuates pulmonary edema and inflammation in lung injury. However, the physiological effects of this drug and their impact on outcomes are poorly characterized. Using serial computed tomography (CT), we tested the hypothesis that imatinib reduces injury severity and improves survival in ventilated rats. Hydrochloric acid (HCl) was instilled in the trachea (pH 1.5, 2.5 mL/kg) of anesthetized, intubated supine rats. Animals were randomized (n = 17 each group) to receive intraperitoneal imatinib or vehicle immediately prior to HCl. All rats then received mechanical ventilation. CT was performed hourly for 4 h. Images were quantitatively analyzed to assess the progression of radiological abnormalities. Injury severity was confirmed via hourly blood gases, serum biomarkers, bronchoalveolar lavage (BAL), and histopathology. Serial blood drug levels were measured in a subset of rats. Imatinib reduced mortality while delaying functional and radiological injury progression: out of 17 rats per condition, 2 control vs. 8 imatinib-treated rats survived until the end of the experiment (P = 0.02). Imatinib attenuated edema after lung injury (P < 0.05), and survival time in both groups was negatively correlated with increased lung mass (R2 = 0.70) as well as other physiological and CT parameters. Capillary leak (BAL protein concentration) was significantly lower in the treated group (P = 0.04). Peak drug concentration was reached after 70 min, and the drug half-life was 150 min. Imatinib decreased both mortality and lung injury severity in mechanically ventilated rats. Pharmacological inhibition of edema could be used during mechanical ventilation to improve the severity and outcome of lung injury.

Population-based return on investment of deploying transient elastography.

OBJECTIVES: To evaluate the cost savings outcomes, from the payer's perspective, of deploying vibration-controlled transient elastography/controlled attenuation parameter (VCTE/CAP) machines for detecting and monitoring fatty liver disease (FLD). STUDY DESIGN: We modeled disease transitions and costs under the current observed pathway and under an alternative pathway in which VCTE/CAP devices are adopted. Marginal savings (or costs) due to implementing the device are derived by comparing the aggregate costs between the 2 pathways. Sources of potential savings are 2-fold. First, VCTE/CAP tests result in early identification of patients with FLD (the majority are currently undiagnosed), allowing for proactive intervention and behavior change to slow the progression of disease in these patients. Second, VCTE/CAP tests can reduce the aggregate volume of some current diagnosis methods, such as liver biopsy, imaging, and laboratory work. METHODS: Our model relied on administrative claims data consisting of 5 million commercial members and 3 million Medicare members to inform baseline statistics on disease prevalence, health care cost and utilization, and disease progression associated with different severities of liver disease. We consulted expert clinical opinion and medical literature to inform our assumptions related to device adoption and use. RESULTS: Scenario testing demonstrated positive net savings within 2 to 3 years after device deployment. Across a 5-year time span, we estimate net savings up to $2.64 per member per month (PMPM) for Medicare payers and up to $1.91 PMPM for commercial payers. CONCLUSIONS: We conclude that deploying VCTE/CAP devices is a financially advantageous solution to address the epidemic of FLD.

Diminishing Efficacy of Prone Positioning With Late Application in Evolving Lung Injury.

OBJECTIVES: It is not known how lung injury progression during mechanical ventilation modifies pulmonary responses to prone positioning. We compared the effects of prone positioning on regional lung aeration in late versus early stages of lung injury. DESIGN: Prospective, longitudinal imaging study. SETTING: Research imaging facility at The University of Pennsylvania (Philadelphia, PA) and Medical and Surgical ICUs at Massachusetts General Hospital (Boston, MA). SUBJECTS: Anesthetized swine and patients with acute respiratory distress syndrome (acute respiratory distress syndrome). INTERVENTIONS: Lung injury was induced by bronchial hydrochloric acid (3.5 mL/kg) in 10 ventilated Yorkshire pigs and worsened by supine nonprotective ventilation for 24 hours. Whole-lung CT was performed 2 hours after hydrochloric acid (Day 1) in both prone and supine positions and repeated at 24 hours (Day 2). Prone and supine images were registered (superimposed) in pairs to measure the effects of positioning on the aeration of each tissue unit. Two patients with early acute respiratory distress syndrome were compared with two patients with late acute respiratory distress syndrome, using electrical impedance tomography to measure the effects of body position on regional lung mechanics. MEASUREMENTS AND MAIN RESULTS: Gas exchange and respiratory mechanics worsened over 24 hours, indicating lung injury progression. On Day 1, prone positioning reinflated 18.9% ± 5.2% of lung mass in the posterior lung regions. On Day 2, position-associated dorsal reinflation was reduced to 7.3% ± 1.5% (p < 0.05 vs Day 1). Prone positioning decreased aeration in the anterior lungs on both days. Although prone positioning improved posterior lung compliance in the early acute respiratory distress syndrome patients, it had no effect in late acute respiratory distress syndrome subjects. CONCLUSIONS: The effects of prone positioning on lung aeration may depend on the stage of lung injury and duration of prior ventilation; this may limit the clinical efficacy of this treatment if applied late.

Randomized controlled trial assessing the effects of xylazine sedation in 2- to 6-week-old dairy calves disbudded with a cautery iron.

The use of local anesthesia and a nonsteroidal anti-inflammatory drug (NSAID) can reduce indicators of pain and inflammation and encourage self-rewarding behavior in calves following disbudding. Although the use of sedation may be recommended as a best practice for disbudding, there is little research in this area. The objective of this study was to evaluate the effects of xylazine sedation in conjunction with a local anesthetic and an NSAID in calves undergoing cautery disbudding. One hundred twenty-two group-housed female and male Holstein calves fed milk with automated feeders, aged 13 to 44 d, were enrolled over 9 replicates and randomly allocated to 1 of 2 treatments: (1) sedated: lidocaine cornual nerve block, 0.5 mg/kg meloxicam (administered subcutaneously) and 0.2 mg/kg xylazine (administered intramuscularly), or (2) nonsedated: lidocaine cornual nerve block and meloxicam. Outcomes collected consisted of feeding behavior (collected using automated milk feeders), latency to drink milk following disbudding, play behavior (induced by adding bedding), lying behavior, mechanical nociceptive threshold (MNT, measured using a pressure force algometer), struggling behavior during disbudding, length of time to administer the nerve block, length of time to disbud, and serum haptoglobin concentrations. Data were analyzed using mixed models with a fixed effect for baseline values and a random effect for trial replicate. Linear regression was used to assess continuous outcomes, logistic regression for binary outcomes, and Poisson and negative binomial models for count data with negative binomial models used if the over dispersion term was significant. There were no detected differences between the treatment groups in mean daily milk consumption in the 72-h following disbudding. Sedated calves had reduced average milk drinking speed from 0 to 24 h and 24 to 48 h following disbudding compared with nonsedated calves, but no difference was detected from 48 to 72 h. Sedated calves had reduced MNT at 0, 60, and 240 min after disbudding, but no differences were detected between groups at 24 h after disbudding. Nonsedated calves had 4.5 times the odds (95% CI: 1.5-13.2) of struggling more than twice during the disbudding procedure compared with sedated calves, and it took less time to administer a nerve block to sedated calves compared with nonsedated. At +3 h, nonsedated calves were 79 times (95% CI: 22.4 to 279.2) more likely to play compared with sedated calves, and 24 h after disbudding, sedated calves were 2 times more likely to play compared with nonsedated calves (95% CI: 0.93-4.3). The results indicate that calves sedated with xylazine for cautery disbudding responded less to painful stimuli (disbudding and MNT) both during and following the procedure and had a higher rate of play behavior 24 h following sedation compared with the nonsedated calves, but xylazine may also have a prolonged carryover effect that affects suckling behavior for 48 h following sedation.

Measuring pulmonary gas exchange using compartment-selective xenon-polarization transfer contrast (XTC) MRI.

PURPOSE: To demonstrate the feasibility of generating red blood cell (RBC) and tissue/plasma (TP)-specific gas-phase (GP) depolarization maps using xenon-polarization transfer contrast (XTC) MR imaging. METHODS: Imaging was performed in three healthy subjects, an asymptomatic smoker, and a chronic obstructive pulmonary disease (COPD) patient. Single-breath XTC data were acquired through a series of three GP images using a 2D multi-slice GRE during a 12 s breath-hold. A series of 8 ms Gaussian inversion pulses spaced 30 ms apart were applied in-between the images to quantify the exchange between the GP and dissolved-phase (DP) compartments. Inversion pulses were either centered on-resonance to generate contrast, or off-resonance to correct for other sources of signal loss. For an alternative scheme, inversions of both RBC and TP resonances were inserted in lieu of off-resonance pulses. Finally, this technique was extended to a multi-breath protocol consistent with tidal breathing, involving 30 consecutive acquisitions. RESULTS: Inversion pulses shifted off-resonance by 20 ppm to mimic the distance between the RBC and TP resonances demonstrated selectivity, and initial GP depolarization maps illustrated stark magnitude and distribution differences between healthy and diseased subjects that were consistent with traditional approaches. CONCLUSION: The proposed DP-compartment selective XTC MRI technique provides information on gas exchange between all three detectable states of xenon in the lungs and is sufficiently sensitive to indicate differences in lung function between the study subjects. Investigated extensions of this approach to imaging schemes that either minimize breath-hold duration or the overall number of breath-holds open avenues for future research to improve measurement accuracy and patient comfort.

Polypharmacy, Medication Possession, and Deprescribing of Potentially Non-Beneficial Drugs in Hospice Patients.

Patients frequently have comorbidities that when combined with their primary diagnosis qualifies the patient for hospice. Consequently, patients are at risk for polypharmacy due to the number of medications prescribed to treat both the underlying conditions and the related symptoms. Polypharmacy is associated with negative consequences, including increased risk for adverse drug events, drug-drug and drug-disease interactions, reduced functional status and falls, multiple geriatric syndromes, medication nonadherence, and increased mortality. Polypharmacy also increases the complexity of medication management for caregivers and contributes to the cost of prescription drugs for hospices and patients. Deprescribing or removing nonbeneficial or ineffective medications can reduce polypharmacy in hospice. We study medication possession ratios and rates of deprescribing of commonly prescribed but potentially nonbeneficial classes of medication using a large hospice pharmacy database. Prevalence of some classes of potentially inappropriate medications is high. We report possession ratios for 10 frequently prescribed classes, and, because death and prescription termination are competing events, we calculate prescription termination rates using Cumulative Incidence Functions. Median duration of antifungal and antiviral medications is brief (5 and 7 days, respectively), while statins and diabetes medications have slow discontinuance rates (median termination durations of 93 and 197 days). Almost all patients with a proton pump inhibitor prescription have the drug for their entire hospice stay. Data from this study identify those drug classes that are commonly deprescribed slowly, suggesting drug classes and diagnoses that hospices may wish to focus on more closely, as they act to limit polypharmacy and reduce prescription costs.

Pulmonary pyruvate metabolism as an index of inflammation and injury in a rat model of acute respiratory distress syndrome.

Increased pulmonary lactate production is correlated with severity of lung injury and outcome in acute respiratory distress syndrome (ARDS) patients. This study was conducted to investigate the relative contributions of inflammation and hypoxia to the lung's metabolic shift to glycolysis in an experimental animal model of ARDS using hyperpolarized (HP) 13 C MRI. Fifty-three intubated and mechanically ventilated male rats were imaged using HP 13 C MRI before, and 1, 2.5 and 4 hours after saline (sham) or hydrochloric acid (HCl; 0.5 ml/kg) instillation in the trachea, followed by protective and nonprotective mechanical ventilation (HCl-PEEP and HCl-ZEEP) or the start of moderate or severe hypoxia (Hyp90 and Hyp75 groups). Pulmonary and cardiac HP lactate-to-pyruvate ratios were compared among groups for different time points. Postmortem histology and immunofluorescence were used to assess lung injury severity and quantify the expression of innate inflammatory markers and local tissue hypoxia. HP pulmonary lactate-to-pyruvate ratio progressively increased in rats with lung injury and moderate hypoxia (HCl-ZEEP), with no significant change in pulmonary lactate-to-pyruvate ratio in noninjured but moderately hypoxic rats (Hyp90). Pulmonary lactate-to-pyruvate ratio was elevated in otherwise healthy lung tissue only in severe systemic hypoxia (Hyp75 group). ex vivo histological and immunopathological assessment further confirmed the link between elevated glycolysis and the recruitment into and presence of activated neutrophils in injured lungs. HP lactate-to-pyruvate ratio is elevated in injured lungs predominantly as a result of increased glycolysis in activated inflammatory cells, but can also increase due to severe inflammation-induced hypoxia.

Feline irradiated diet-induced demyelination; a model of the neuropathology of sub-acute combined degeneration?

Irradiation of food at 50-55 kGy results in a profound, chronic demyelinating-remyelinating disease of the entire central nervous system (CNS) in cats, named Feline Irradiated Diet-Induced Demyelination (FIDID). This study examines the early stages of demyelination and long-term consequences of demyelination and remyelination on axon survival or loss. Myelin vacuolation is the primary defect leading to myelin breakdown, demyelination then prompt remyelination in the spinal cord and brain. There is no evidence of oligodendrocyte death. The spinal cord dorsal column is initially spared yet eventually becomes severely demyelinated with subsequent loss of axons in the core and then surface of the fasciculus gracilis. However remyelination of the sub-pial axons in the dorsal column results in their protection. While there was a lack of biochemical evidence of Vitamin B12 deficiency, the pathological similarities of FIDID with sub-acute combined degeneration (SCD) led us to explore treatment with Vitamin B12. Treatment led to recovery or improvement in some cats and neurologic relapse on cessation of B12 therapy. While the reason that irradiated food is myelinotoxic in the cat remains unresolved, nonetheless the neuropathological changes match exactly what is seen in SCD and its models and provide an ideal model to study the cellular and molecular basis of remyelination.

Discovery of an Orally Bioavailable Pan αv Integrin Inhibitor for Idiopathic Pulmonary Fibrosis.

The heterodimeric transmembrane αv integrin receptors have recently emerged as potential targets for the treatment of idiopathic pulmonary fibrosis. Herein, we describe how subtle modifications of the central aromatic ring of a series of phenylbutyrate-based antagonists of the vitronectin receptors αvß3 and αvß5 significantly change the biological activities against αvß6 and αvß8. This resulted in the discovery of a pan αv antagonist (compound 39, 4-40 nM for the integrin receptors named above) possessing excellent oral pharmacokinetic properties in rats (with a clearance of 7.6 mL/(min kg) and a bioavailability of 97%).

Quantification of Ventilation and Gas Uptake in Free-Breathing Mice With Hyperpolarized 129Xe MRI.

Hyperpolarized 129Xe magnetic resonance imaging is a powerful modality capable of assessing lung structure and function. While it has shown promise as a clinical tool for the longitudinal assessment of lung function, its utility as an investigative tool for animal models of pulmonary diseases is limited by the necessity of invasive intubation and mechanical ventilation procedures. In this paper, we overcame this limitation by developing a gas delivery system and implementing a set of imaging schemes to acquire high-resolution gas- and dissolved-phase images in free-breathing mice. Gradient echo pulse sequences were used to acquire both high- and low-resolution gas-phase images, and regional fractional ventilation was quantified by comparing signal buildup among low-resolution gas-phase images acquired at two flip-angles. Dissolved-phase images were acquired using both ultra-short echo time and chemical shift imaging sequences with discrete sets of flip-angle/repetition time combinations to visualize gas uptake and distribution throughout the body. Spectral features distinct to various anatomical regions were identified in images acquired using the latter sequence and were used for the quantification of gas arrival times for respective compartments.

Application of Machine Learning to Identify Clustering of Cardiometabolic Risk Factors in U.S. Adults.

Aims: The aim of this study is to compare some machine learning methods with traditional statistical parametric analyses using logistic regression to investigate the relationship of risk factors for diabetes and cardiovascular (cardiometabolic risk) for U.S. adults using a cross-sectional data from participants in a wellness improvement program. Methods: Logistic regression was used to find the relationship between individual risk factors, predictor and cardiometabolic risk. Supervised machine learning methods were used to predict risk and produce a ranking of variables' importance. A clustering method was used to identify subpopulations of interest. Predictors were divided into those that are nonmodifiable and those that are modifiable. Results: The population comprised 217,254 adults of whom 8.1% had diabetes. Using logistic regression, six variables were identified to be negatively related and eleven were positively related to cardiometabolic risk. Three supervised machine learning classifiers (random forest, gradient boosting, and bagging) were applied with average AUC to be 0.806. Each classifier also produced a ranking of variables' importance. Four subgroups were identified with a k-medoid clustering algorithm, which were mainly distinguished by gender and diabetes status. Conclusions: The study illustrates that machine learning is an important addition to traditional logistic regression in terms of identifying important cardiometabolic risk factors and ranking their importance and the potential for interventions based on lifestyle and medications at an individual level.

Effects of a Population Health Community-Based Palliative Care Program on Cost and Utilization.

Background: New population health community-based models of palliative care can result in more compassionate, affordable, and sustainable high-quality care. Objectives: We evaluated utilization and cost outcomes of a standardized, population health community-based palliative care program provided by nurses and social workers. Design: We conducted a retrospective propensity-adjusted study to quantify cost savings and resource utilization associated with a community-based palliative care program. We analyzed claims data from a Medicare Advantage (MA) plan and used a proprietary predictive model to identify 804 members at high risk for overmedicalized end-of-life care. We enrolled 204 members in the palliative care program and compared them with 600 who received standard, telephonic, health plan case management. We excluded members with fewer than two months of enrolled experience or those with insufficient data for analysis, leaving 176 members in the study group and 570 in the control group for evaluation. We compared differences in utilization and costs (medical and pharmacy), hospital admissions, bed days (acute and intensive care unit [ICU]), and emergency department visits. Setting/Subjects: A 30,000-member MA plan and a health system in Central Ohio between October 2015 and June 2016. Results: Members who received community-based palliative care showed a statistically significant 20% reduction in total medical costs ($619 per enrolled member per month), 38% reduction in ICU admissions, 33% reduction in hospital admissions, and 12% reduction in hospital days. Conclusion: A structured nurse and social work model of community-based palliative care using a predictive model to identify MA candidates for intervention can reduce utilization and medical costs.

Measurement of Regional 2D Gas Transport Efficiency in Rabbit Lung Using Hyperpolarized 129Xe MRI.

While hyperpolarized xenon-129 (HXe) MRI offers a wide array of tools for assessing functional aspects of the lung, existing techniques provide only limited quantitative information about the impact of an observed pathology on overall lung function. By selectively destroying the alveolar HXe gas phase magnetization in a volume of interest and monitoring the subsequent decrease in the signal from xenon dissolved in the blood inside the left ventricle of the heart, it is possible to directly measure the contribution of that saturated lung volume to the gas transport capacity of the entire lung. In mechanically ventilated rabbits, we found that both xenon gas transport and transport efficiency exhibited a gravitation-induced anterior-to-posterior gradient that disappeared or reversed direction, respectively, when the animal was turned from supine to prone position. Further, posterior ventilation defects secondary to acute lung injury could be re-inflated by applying positive end expiratory pressure, although at the expense of decreased gas transport efficiency in the anterior volumes. These findings suggest that our technique might prove highly valuable for evaluating lung transplants and lung resections, and could improve our understanding of optimal mechanical ventilator settings in acute lung injury.

A Model for Predicting Future FEV1 Decline in Smokers Using Hyperpolarized 3He Magnetic Resonance Imaging.

RATIONALE AND OBJECTIVES: The purpose of this study was to assess the effectiveness of hyperpolarized helium-3 magnetic resonance (MR)-based imaging markers in predicting future forced expiratory volume in one second decline/chronic obstructive pulmonary disorder progression in smokers compared to current diagnostic techniques. MATERIALS AND METHODS: Total 60 subjects (15 nonsmokers and 45 smokers) participated in both baseline and follow-up visits (∼1.4 years apart). At both visits, subjects completed pulmonary function testing, a six-minute walk test , and the St. George Respiratory Questionnaire. Using helium-3 MR imaging, means (M) and standard deviations (H) of oxygen tension (PAO2), fractional ventilation, and apparent diffusion coefficient were calculated across 12 regions of interest in the lungs. Subjects who experienced FEV1 decline >100 mL/year were deemed "decliners," while those who did not were deemed "sustainers." Nonimaging and imaging prediction models were generated through a logistic regression model, which utilized measurements from sustainers and decliners. RESULTS: The nonimaging prediction model included the St. George Respiratory Questionnaire total score, diffusing capacity of carbon monoxide by the alveolar volume (DLCO/VA), and distance walked in a six-minute walk test. A receiving operating character curve for this model yielded a sensitivity of 75% and specificity of 68% with an overall area under the curve of 65%. The imaging prediction model generated following the same methodology included ADCH, FVH, and PAO2H. The resulting receiving operating character curve yielded a sensitivity of 87.5%, specificity of 82.8%, and an area under the curve of 89.7%. CONCLUSION: The imaging predication model generated from measurements obtained during 3He MR imaging is better able to predict future FEV1 decline compared to one based on current clinical tests and demographics. The imaging model's superiority appears to arise from its ability to distinguish well-circumscribed, severe disease from a more uniform distribution of moderately altered lung function, which is more closely associated with subsequent FEV1 decline.

Accuracy of multiparametric magnetic resonance imaging to detect significant prostate cancer and index lesion location.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) of the prostate appears to improve prostate cancer detection, but studies comparing mpMRI to histopathology at the time of radical prostatectomy (RP) are lacking. This retrospective study determined the accuracy of mpMRI predicting Gleason score and index lesion location at the time of RP, the current gold standard for diagnosis. METHODS: Between April 2013 and April 2016, a database of all men aged more than 40 years who underwent RP after positive transrectal ultrasound biopsy by an experienced urological surgeon was collated at a single regional centre. This was cross-referenced with a database of all men who had mpMRIs performed at a single centre and reported according to Prostate Imaging Reporting and Data System (PI-RADS version 1) during this period to generate a sample size of 64 men. A Spearman's rho test was utilized to calculate correlation. RESULTS: Median age of patients was 64 years, the median prostate-specific antigen at RP was 6.22 ng/mL. mpMRI was positive (≥PI-RADS 3) in 85.9% of patients who underwent RP. More than 92% of participants had Gleason ≥7 disease. A positive relationship between mpMRI prostate PI-RADS score and RP cancer volume was demonstrated. An anatomical location correlation calculated in octants was found to be 89.1% accurate. CONCLUSION: mpMRI accurately detects prostate cancer location and severity when compared with gold standard histopathology at the time of RP. It thus has an important role in planning for future prostate biopsy and cancer treatment.

Assessment of Pulmonary Gas Transport in Rabbits Using Hyperpolarized Xenon-129 Magnetic Resonance Imaging.

Many forms of lung disease manifest themselves as pathological changes in the transport of gas to the circulatory system, yet the difficulty of imaging this process remains a central obstacle to the comprehensive diagnosis of lung disorders. Using hyperpolarized xenon-129 as a surrogate marker for oxygen, we derived the temporal dynamics of gas transport from the ratio of two lung images obtained with different timing parameters. Additionally, by monitoring changes in the total hyperpolarized xenon signal intensity in the left side of the heart induced by depletion of xenon signal in the alveolar airspaces of interest, we quantified the contributions of selected lung volumes to the total pulmonary gas transport. In a rabbit model, we found that it takes at least 200 ms for xenon gas to enter the lung tissue and travel the distance from the airspaces to the heart. Additionally, our method shows that both lungs contribute fairly equally to the gas transport in healthy rabbits, but that this ratio changes in a rabbit model of acid aspiration. These results suggest that hyperpolarized xenon-129 MRI may improve our ability to measure pulmonary gas transport and detect associated pathological changes.

Rapid assessment of pulmonary gas transport with hyperpolarized 129Xe MRI using a 3D radial double golden-means acquisition with variable flip angles.

PURPOSE: To demonstrate the feasibility of using a 3D radial double golden-means acquisition with variable flip angles to monitor pulmonary gas transport in a single breath hold with hyperpolarized xenon-129 MRI. METHODS: Hyperpolarized xenon-129 MRI scans with interleaved gas-phase and dissolved-phase excitations were performed using a 3D radial double golden-means acquisition in mechanically ventilated rabbits. The flip angle was either held fixed at 15 ° or 5 °, or it was varied linearly in ascending or descending order between 5 ° and 15 ° over a sampling interval of 1000 spokes. Dissolved-phase and gas-phase images were reconstructed at high resolution (32 × 32 × 32 matrix size) using all 1000 spokes, or at low resolution (22 × 22 × 22 matrix size) using 400 spokes at a time in a sliding-window fashion. Based on these sliding-window images, relative change maps were obtained using the highest mean flip angle as the reference, and aggregated pixel-based changes were tracked. RESULTS: Although the signal intensities in the dissolve-phase maps were mostly constant in the fixed flip-angle acquisitions, they varied significantly as a function of average flip angle in the variable flip-angle acquisitions. The latter trend reflects the underlying changes in observed dissolve-phase magnetization distribution due to pulmonary gas uptake and transport. CONCLUSION: 3D radial double golden-means acquisitions with variable flip angles provide a robust means for rapidly assessing lung function during a single breath hold, thereby constituting a particularly valuable tool for imaging uncooperative or pediatric patient populations.