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Social synchronization of circadian rhythmicity in female mice depends on the number of cohabiting animals

Wed, 07/20/2016 - 9:49am

Communal animals often engage in group activities that require temporal synchrony among its members, including synchrony on the circadian timescale. The principles and conditions that foster such collective synchronization are not understood, but existing literature hints that the number of interacting individuals may be a critical factor. We tested this by recording individual circadian body temperature rhythms of female house mice housed singly, in twos (pairs), or in groups of five (quintets) in constant darkness; determining the daily phases of the circadian peak for each animal; and then calculating the cycle-to-cycle phase relationship between cohabiting animals over time. Significant temporal coherence was observed in quintets: the proportion of quintets (4/7), but not pairs (2/8), that became synchronized was greater than could be achieved by the complete simulated reassortment of all individuals. We speculate that the social coupling of individual circadian clocks of group members may be adaptive under certain conditions, and we propose that optimal group sizes in nature may depend not only on species-specific energetics, spatial behaviour and natural history but also on the mathematics of synchronizing assemblies of weakly coupled animal oscillators.

Age and sex differences in long-term outcomes following implantable cardioverter-defibrillator placement in contemporary clinical practice: findings from the Cardiovascular Research Network

Wed, 07/20/2016 - 9:48am

BACKGROUND: Patient sex and age may influence rates of death after receiving an implantable cardioverter-defibrillator for primary prevention. Differences in outcomes other than mortality and whether these differences vary by heart failure symptoms, etiology, and left ventricular ejection fraction are not well characterized.

METHODS AND RESULTS: We studied 2954 patients with left ventricular ejection fraction < /=0.35 undergoing first-time implantable cardioverter-defibrillator for primary prevention within the Cardiovascular Research Network; 769 patients (26%) were women, and 2827 (62%) were aged > 65 years. In a median follow-up of 2.4 years, outcome rates per 1000 patient-years were 109 for death, 438 for hospitalization, and 111 for heart failure hospitalizations. Procedure-related complications occurred in 8.36%. In multivariable models, women had significantly lower risks of death (hazard ratio 0.67, 95% CI 0.56 to 0.80) and heart failure hospitalization (hazard ratio 0.82, 95% CI 0.68 to 0.98) and higher risks for complications (hazard ratio 1.38, 95% CI 1.01 to 1.90) than men; patients aged > 65 years had higher risks of death (hazard ratio 1.55, 95% CI 1.30 to 1.86) and heart failure hospitalization (hazard ratio 1.25, 95% CI 1.05 to 1.49) than younger patients. Age and sex differences were generally consistent in strata according to symptoms, etiology, and severity of left ventricular systolic dysfunction, except the higher risk of complications in women, which differed by New York Heart Association classification (P=0.03 for sex-New York Heart Association interaction), and the risk of heart failure hospitalization in older patients, which differed by etiology of heart failure (P=0.05 for age-etiology interaction).

CONCLUSIONS: The burden of adverse outcomes after receipt of an implantable cardioverter-defibrillator for primary prevention is substantial and varies according to patient age and sex. These differences in outcome generally do not vary according to baseline heart failure characteristics.

Patient Portals: An Underused Resource for Improving Patient Engagement

Wed, 07/20/2016 - 9:48am

The potential of patient portals to improve patient engagement and health outcomes has been discussed for more than a decade. The slow growth in patient portal adoption rates among patients and providers in the United States, despite external incentives, indicates that this is a complex issue. We examined evidence of patient portal use and effects with a focus on the pulmonary domain. We found a paucity of studies of patient portal use in pulmonary practice, and highlight gaps for future research. We also report on the experience of a pulmonary department using a patient portal to highlight the potential of these systems. Inc.

Hepatocellular Carcinoma Recurrence Pattern Following Liver Transplantation and a Suggested Surveillance Algorithm

Tue, 07/19/2016 - 3:28pm

Purpose: Evaluate the recurrence pattern of hepatocellular carcinoma (HCC) following liver transplantation.

Materials and Methods: A total of 54 patients underwent liver transplantation for HCC; 9 patients developed biopsy proven recurrent HCC (16.6%). The site of HCC recurrence along with other factors were analyzed.

Results: Seven patients were diagnosed with HCC prior to liver transplantation and 2 patients had incidental HCC in the explanted liver. Two patients had locoregional recurrence, 4 patients had distant metastasis and 3 patients had synchronous locoregional recurrence and distant metastasis.

Conclusion: A significant proportion of HCC recurrence following liver transplantation is extrahepatic.

Case of the Week: A 51-year-old Man with Headaches and Visual Disturbances

Tue, 07/19/2016 - 3:27pm

"Case of the Week" for the American Journal of Neuroradiology, with the following description: Sagittal T1WI pre- (A) and postcontrast (B) show a large, lobulated, heterogeneously-enhancing pituitary mass that expands the sella and demonstrates a suprasellar extension. Axial (C) and sagittal (D) T2WI demonstrate diffuse thickening of the calvarium with heterogeneous marrow signal. Axial (E) and coronal (F) noncontrast CT through the level of the parathyroid gland demonstrate hypodense nodules posterior and inferior to the thyroid lobes (arrows).

MCQs in Neuroradiology: Brain and Physics

Tue, 07/19/2016 - 3:27pm

Version 1.4 of this book contains 500 multiple choice questions (MCQs) in Neuroradiology dealing with subjects of brain and physics, to assist in preparing for certification exams. The MCQs are organized into easy, intermediate and difficult categories. The answer page covers not only the topic of the MCQ but also the related material. The MCQs have been prepared mostly from the review articles especially RadioGraphics.

Discovery and Reuse of Open Datasets: An Exploratory Study

Tue, 07/19/2016 - 8:56am

Objective: This article analyzes twenty cited or downloaded datasets and the repositories that house them, in order to produce insights that can be used by academic libraries to encourage discovery and reuse of research data in institutional repositories.

Methods: Using Thomson Reuters’ Data Citation Index and repository download statistics, we identified twenty cited/downloaded datasets. We documented the characteristics of the cited/downloaded datasets and their corresponding repositories in a self-designed rubric. The rubric includes six major categories: basic information; funding agency and journal information; linking and sharing; factors to encourage reuse; repository characteristics; and data description.

Results: Our small-scale study suggests that cited/downloaded datasets generally comply with basic recommendations for facilitating reuse: data are documented well; formatted for use with a variety of software; and shared in established, open access repositories. Three significant factors also appear to contribute to dataset discovery: publishing in discipline-specific repositories; indexing in more than one location on the web; and using persistent identifiers. The cited/downloaded datasets in our analysis came from a few specific disciplines, and tended to be funded by agencies with data publication mandates.

Conclusions: The results of this exploratory research provide insights that can inform academic librarians as they work to encourage discovery and reuse of institutional datasets. Our analysis also suggests areas in which academic librarians can target open data advocacy in their communities in order to begin to build open data success stories that will fuel future advocacy efforts.

TAD disruption as oncogenic driver

Thu, 07/14/2016 - 9:21pm

Topologically Associating Domains (TADs) are conserved during evolution and play roles in guiding and constraining long-range regulation of gene expression. Disruption of TAD boundaries results in aberrant gene expression by exposing genes to inappropriate regulatory elements. Recent studies have shown that TAD disruption is often found in cancer cells and contributes to oncogenesis through two mechanisms. One mechanism locally disrupts domains by deleting or mutating a TAD boundary leading to fusion of the two adjacent TADs. The other mechanism involves genomic rearrangements that break up TADs and creates new ones without directly affecting TAD boundaries. Understanding the mechanisms by which TADs form and control long-range chromatin interactions will therefore not only provide insights into the mechanism of gene regulation in general, but will also reveal how genomic rearrangements and mutations in cancer genomes can lead to misregulation of oncogenes and tumor suppressors.

Local Genome Topology Can Exhibit an Incompletely Rewired 3D-Folding State during Somatic Cell Reprogramming

Thu, 07/14/2016 - 9:21pm

Pluripotent genomes are folded in a topological hierarchy that reorganizes during differentiation. The extent to which chromatin architecture is reconfigured during somatic cell reprogramming is poorly understood. Here we integrate fine-resolution architecture maps with epigenetic marks and gene expression in embryonic stem cells (ESCs), neural progenitor cells (NPCs), and NPC-derived induced pluripotent stem cells (iPSCs). We find that most pluripotency genes reconnect to target enhancers during reprogramming. Unexpectedly, some NPC interactions around pluripotency genes persist in our iPSC clone. Pluripotency genes engaged in both "fully-reprogrammed" and "persistent-NPC" interactions exhibit over/undershooting of target expression levels in iPSCs. Additionally, we identify a subset of "poorly reprogrammed" interactions that do not reconnect in iPSCs and display only partially recovered, ESC-specific CTCF occupancy. 2i/LIF can abrogate persistent-NPC interactions, recover poorly reprogrammed interactions, reinstate CTCF occupancy, and restore expression levels. Our results demonstrate that iPSC genomes can exhibit imperfectly rewired 3D-folding linked to inaccurately reprogrammed gene expression.

Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma

Thu, 07/14/2016 - 9:21pm

BACKGROUND: Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction.

METHODS: We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma.

RESULTS: Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P < 0.001 for all comparisons). At the last spirometric measurement (mean [+/-SD] age, 26.0+/-1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P < 0.001).

CONCLUSIONS: Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; number, NCT00000575.).

A Caenorhabditis elegans Genome-Scale Metabolic Network Model

Thu, 07/14/2016 - 9:21pm

Caenorhabditis elegans is a powerful model to study metabolism and how it relates to nutrition, gene expression, and life history traits. However, while numerous experimental techniques that enable perturbation of its diet and gene function are available, a high-quality metabolic network model has been lacking. Here, we reconstruct an initial version of the C. elegans metabolic network. This network model contains 1,273 genes, 623 enzymes, and 1,985 metabolic reactions and is referred to as iCEL1273. Using flux balance analysis, we show that iCEL1273 is capable of representing the conversion of bacterial biomass into C. elegans biomass during growth and enables the predictions of gene essentiality and other phenotypes. In addition, we demonstrate that gene expression data can be integrated with the model by comparing metabolic rewiring in dauer animals versus growing larvae. iCEL1273 is available at a dedicated website ( and will enable the unraveling of the mechanisms by which different macro- and micronutrients contribute to the animal's physiology.

Design of a Multi-Pinhole Collimator for I-123 DaTscan Imaging on Dual-Headed SPECT Systems in Combination with a Fan-Beam Collimator

Thu, 07/14/2016 - 8:59pm

For the 2011 FDA approved Parkinson's Disease (PD) SPECT imaging agent I-123 labeled DaTscan, the volume of interest (VOI) is the interior portion of the brain. However imaging of the occipital lobe is also required with PD for calculation of the striatal binding ratio (SBR), a parameter of significance in early diagnosis, differentiation of PD from other disorders with similar clinical presentations, and monitoring progression. Thus we propose the usage of a combination of a multi-pinhole (MPH) collimator on one head of the SPECT system and a fan-beam on the other. The MPH would be designed to provide high resolution and sensitivity for imaging of the interior portion of the brain. The fan-beam collimator would provide lower resolution but complete sampling of the brain addressing data sufficiency and allowing a volume-of-interest to be defined over the occipital lobe for calculation of SBR's. Herein we focus on the design of the MPH component of the combined system. Combined reconstruction will be addressed in a subsequent publication. An analysis of 46 clinical DaTscan studies was performed to provide information to define the VOI, and design of a MPH collimator to image this VOI. The system spatial resolution for the MPH was set to 4.7 mm, which is comparable to that of clinical PET systems, and significantly smaller than that of fan-beam collimators employed in SPECT. With this set, we compared system sensitivities for three aperture array designs, and selected the 3 x 3 array due to it being the highest of the three. The combined sensitivity of the apertures for it was similar to that of an ultra-high resolution fan-beam (LEUHRF) collimator, but smaller than that of a high-resolution fan-beam collimator (LEHRF). On the basis of these results we propose the further exploration of this design through simulations, and the development of combined MPH and fan-beam reconstruction.

Modeling the respiratory motion of solitary pulmonary nodules and determining the impact of respiratory motion on their detection in SPECT imaging

Thu, 07/14/2016 - 8:58pm

The objectives of this investigation were to model the respiratory motion of solitary pulmonary nodules (SPN) and then use this model to determine the impact of respiratory motion on the localization and detection of small SPN in SPECT imaging for four reconstruction strategies. The respiratory motion of SPN was based on that of normal anatomic structures in the lungs determined from breath-held CT images of a volunteer acquired at two different stages of respiration. End-expiration (EE) and time-averaged (Frame Av) non-uniform-B-spline cardiac torso (NCAT) digital-anthropomorphic phantoms were created using this information for respiratory motion within the lungs. SPN were represented as 1 cm diameter spheres which underwent linear motion during respiration between the EE and end-inspiration (EI) time points. The SIMIND Monte Carlo program was used to produce SPECT projection data simulating Tc-99m depreotide (NeoTect) imaging. The projections were reconstructed using 1) no correction (NC), 2) attenuation correction (AC), 3) resolution compensation (RC), and 4) attenuation correction, scatter correction, and resolution compensation (AC_SC_RC). A human-observer localization receiver operating characteristics (LROC) study was then performed to determine the difference in localization and detection accuracy with and without the presence of respiratory motion. The LROC comparison determined that respiratory motion degrades tumor detection for all four reconstruction strategies, thus correction for SPN motion would be expected to improve detection accuracy. The inclusion of RC in reconstruction improved detection accuracy for both EE and Frame Av over NC and AC. Also the magnitude of the impact of motion was least for AC_SC_RC.

LROC Investigation of Three Strategies for Reducing the Impact of Respiratory Motion on the Detection of Solitary Pulmonary Nodules in SPECT

Thu, 07/14/2016 - 8:58pm

The objective of this investigation was to determine the effectiveness of three motion reducing strategies in diminishing the degrading impact of respiratory motion on the detection of small solitary pulmonary nodules (SPN) in single photon emission computed tomographic (SPECT) imaging in comparison to a standard clinical acquisition and the ideal case of imaging in the absence of respiratory motion. To do this non-uniform rational B-spline cardiac-torso (NCAT) phantoms based on human-volunteer CT studies were generated spanning the respiratory cycle for a normal background distribution of Tc-99m NeoTect. Similarly, spherical phantoms of 1.0 cm diameter were generated to model small SPN for each of 150 uniquely located sites within the lungs whose respiratory motion was based on the motion of normal structures in the volunteer CT studies. The SIMIND Monte Carlo program was used to produce SPECT projection data from these. Normal and single-lesion containing SPECT projection sets with a clinically realistic Poisson noise level were created for the cases of: 1) the end-expiration (EE) frame with all counts, 2) respiration-averaged motion with all counts, 3) one-fourth of the 32 frames centered around EE (Quarter-Binning), 4) one-half of the 32 frames centered around EE (Half-Binning), and 5) eight temporally binned frames spanning the respiratory cycle. Each of the sets of combined projection data were reconstructed with RBI-EM with system spatial-resolution compensation (RC). Based on the known motion for each of the 150 different lesions, the reconstructed volumes of respiratory bins were shifted so as to superimpose the locations of the SPN onto that in the first bin (Reconstruct and Shift). Five human-observers performed localization receiver operating characteristics (LROC) studies of SPN detection. The observer results were analyzed for statistical significance differences in SPN detection accuracy among the three correction strategies, the standard acquisition, and the ideal case of the absence of respiratory motion. Our human-observer LROC determined that Quarter-Binning and Half-Binning strategies resulted in SPN detection accuracy statistically significantly below (P < 0.05) that of standard clinical acquisition, whereas the Reconstruct and Shift strategy resulted in a detection accuracy not statistically significantly different from that of the ideal case. This investigation demonstrates that tumor detection based on acquisitions associated with less than all the counts which could potentially be employed may result in poorer detection despite limiting the motion of the lesion. The Reconstruct and Shift method results in tumor detection that is equivalent to ideal motion correction.

Ultrasonography of the scrotum in adults

Thu, 07/14/2016 - 8:58pm

Ultrasonography is the ideal noninvasive imaging modality for evaluation of scrotal abnormalities. It is capable of differentiating the most important etiologies of acute scrotal pain and swelling, including epididymitis and testicular torsion, and is the imaging modality of choice in acute scrotal trauma. In patients presenting with palpable abnormality or scrotal swelling, ultrasonography can detect, locate, and characterize both intratesticular and extratesticular masses and other abnormalities. A 12-17 MHz high frequency linear array transducer provides excellent anatomic detail of the testicles and surrounding structures. In addition, vascular perfusion can be easily assessed using color and spectral Doppler analysis. In most cases of scrotal disease, the combination of clinical history, physical examination, and information obtained with ultrasonography is sufficient for diagnostic decision-making. This review covers the normal scrotal anatomy as well as various testicular and scrotal lesions.

Monotherapy with stenting in subarachnoid hemorrhage (SAH) after middle cerebral artery dissection

Thu, 07/14/2016 - 8:58pm

Isolated middle cerebral artery dissection is a rare clinical entity, with descriptions limited to a few case reports and case series. Symptomatic dissection in the anterior circulation can present as an ischemic stroke in a young population; however, it is rarely associated with subarachnoid hemorrhage. We describe a young patient who presented with acute headache from a subarachnoid hemorrhage that was ultimately determined to be due to a vascular dissection in the middle cerebral artery. The initial angiogram showed vascular irregularities in this area with stenosis. Repeat imaging 4 days after presentation identified a pseudoaneurysm proximal to the stenosis. The patient was successfully treated with a self-expanding nitinol stent and followed up with serial angiography during postoperative recovery in the hospital; additional angiograms were performed approximately 1 and 6 months after treatment. Serial angiograms demonstrated incremental healing of the dissection. The patient was discharged and remains neurologically intact at the 6-month follow-up.

Photon-counting hexagonal pixel array CdTe detector: Spatial resolution characteristics for image-guided interventional applications

Thu, 07/14/2016 - 8:58pm

PURPOSE: High-resolution, photon-counting, energy-resolved detector with fast-framing capability can facilitate simultaneous acquisition of precontrast and postcontrast images for subtraction angiography without pixel registration artifacts and can facilitate high-resolution real-time imaging during image-guided interventions. Hence, this study was conducted to determine the spatial resolution characteristics of a hexagonal pixel array photon-counting cadmium telluride (CdTe) detector.

METHODS: A 650 mum thick CdTe Schottky photon-counting detector capable of concurrently acquiring up to two energy-windowed images was operated in a single energy-window mode to include photons of 10 keV or higher. The detector had hexagonal pixels with apothem of 30 mum resulting in pixel pitch of 60 and 51.96 mum along the two orthogonal directions. The detector was characterized at IEC-RQA5 spectral conditions. Linear response of the detector was determined over the air kerma rate relevant to image-guided interventional procedures ranging from 1.3 nGy/frame to 91.4 muGy/frame. Presampled modulation transfer was determined using a tungsten edge test device. The edge-spread function and the finely sampled line spread function accounted for hexagonal sampling, from which the presampled modulation transfer function (MTF) was determined. Since detectors with hexagonal pixels require resampling to square pixels for distortion-free display, the optimal square pixel size was determined by minimizing the root-mean-squared-error of the aperture functions for the square and hexagonal pixels up to the Nyquist limit.

RESULTS: At Nyquist frequencies of 8.33 and 9.62 cycles/mm along the apothem and orthogonal to the apothem directions, the modulation factors were 0.397 and 0.228, respectively. For the corresponding axis, the limiting resolution defined as 10% MTF occurred at 13.3 and 12 cycles/mm, respectively. Evaluation of the aperture functions yielded an optimal square pixel size of 54 mum. After resampling to 54 mum square pixels using trilinear interpolation, the presampled MTF at Nyquist frequency of 9.26 cycles/mm was 0.29 and 0.24 along the orthogonal directions and the limiting resolution (10% MTF) occurred at approximately 12 cycles/mm. Visual analysis of a bar pattern image showed the ability to resolve close to 12 line-pairs/mm and qualitative evaluation of a neurovascular nitinol-stent showed the ability to visualize its struts at clinically relevant conditions.

CONCLUSIONS: Hexagonal pixel array photon-counting CdTe detector provides high spatial resolution in single-photon counting mode. After resampling to optimal square pixel size for distortion-free display, the spatial resolution is preserved. The dual-energy capabilities of the detector could allow for artifact-free subtraction angiography and basis material decomposition. The proposed high-resolution photon-counting detector with energy-resolving capability can be of importance for several image-guided interventional procedures as well as for pediatric applications.

Improved frame-based estimation of head motion in PET brain imaging

Thu, 07/14/2016 - 8:58pm

PURPOSE: Head motion during PET brain imaging can cause significant degradation of image quality. Several authors have proposed ways to compensate for PET brain motion to restore image quality and improve quantitation. Head restraints can reduce movement but are unreliable; thus the need for alternative strategies such as data-driven motion estimation or external motion tracking. Herein, the authors present a data-driven motion estimation method using a preprocessing technique that allows the usage of very short duration frames, thus reducing the intraframe motion problem commonly observed in the multiple frame acquisition method.

METHODS: The list mode data for PET acquisition is uniformly divided into 5-s frames and images are reconstructed without attenuation correction. Interframe motion is estimated using a 3D multiresolution registration algorithm and subsequently compensated for. For this study, the authors used 8 PET brain studies that used F-18 FDG as the tracer and contained minor or no initial motion. After reconstruction and prior to motion estimation, known motion was introduced to each frame to simulate head motion during a PET acquisition. To investigate the trade-off in motion estimation and compensation with respect to frames of different length, the authors summed 5-s frames accordingly to produce 10 and 60 s frames. Summed images generated from the motion-compensated reconstructed frames were then compared to the original PET image reconstruction without motion compensation.

RESULTS: The authors found that our method is able to compensate for both gradual and step-like motions using frame times as short as 5 s with a spatial accuracy of 0.2 mm on average. Complex volunteer motion involving all six degrees of freedom was estimated with lower accuracy (0.3 mm on average) than the other types investigated. Preprocessing of 5-s images was necessary for successful image registration. Since their method utilizes nonattenuation corrected frames, it is not susceptible to motion introduced between CT and PET acquisitions.

CONCLUSIONS: The authors have shown that they can estimate motion for frames with time intervals as short as 5 s using nonattenuation corrected reconstructed FDG PET brain images. Intraframe motion in 60-s frames causes degradation of accuracy to about 2 mm based on the motion type.

Evaluation of oxygen sensitivity of hyperpolarized helium imaging for the detection of pulmonary ischemia

Thu, 07/14/2016 - 8:58pm

PURPOSE: In this study, a new model of pulmonary embolism in rats was developed and tested, to examine if hyperpolarized (HP) (3) He MR images can measure impairment of the exchange of oxygen from the airspaces to the blood during pulmonary embolism.

METHODS: HP (3) He MRI was used to image six treatment-group rats in which a branch of the pulmonary artery was embolized, and six control-group rats. HP (3) He MR images were used to calculate the initial partial pressure of oxygen (pO ) and the rate of oxygen depletion (R) in rat lungs.

RESULTS: The pO was significantly higher in the ischemic lung than in the contralateral normal side, and pO was significantly higher in the ischemic lung than in both sides of the control lungs. Mean R in ischemic lungs was significantly lower than in the contralateral lungs, and mean R in ischemic lungs was also significantly lower than in both control lungs.

CONCLUSION: These results demonstrate that pO and R, as measured by the T1 decay of HP (3) He, are sensitive to pulmonary ischemia in rats, confirming the findings in studies performed in large animal models of pulmonary ischemia.