Complications After Renal Mass Biopsy: Frequency, Nature, Timing, and Associated Characteristics.

BACKGROUND. Observation periods after renal mass biopsy (RMB) range from 1 hour to overnight hospitalization. Short observation may improve efficiency by allowing use of the same recovery bed and other resources for RMBs in additional patients. OBJECTIVE. The purpose of this study was to evaluate the frequency, timing, and nature of complications after RMB, as well as to identify characteristics associated with such complications. METHODS. This retrospective study included 576 patients (mean age, 64.9 years; 345 men, 231 women) who underwent percutaneous ultrasound- or CT-guided RMB at one of three hospitals, performed by 22 radiologists, between January 1, 2008, and June 1, 2020. The EHR was reviewed to identify postbiopsy complications, which were classified as bleeding-related or non-bleeding-related and as acute (< 24 hours), subacute (24 hours to 30 days), or delayed (> 30 days). Deviations from normal clinical management (analgesia, unplanned laboratory testing, or additional imaging) were identified. RESULTS. Acute and subacute complications occurred after 3.6% (21/576) and 0.7% (4/576) of RMBs, respectively. No delayed complication or patient death occurred. A total of 76.2% (16/21) of acute complications were bleeding-related. A deviation from normal clinical management occurred after 1.6% (9/551) of RMBs that had no associated postbiopsy complication. Among the 16 patients with bleeding-related acute complications, all experienced a deviation, with mean time to deviation of 56 ± 47 (SD) minutes (range, 10-162 minutes; ≤ 120 minutes in 13/16 patients). The five non-bleeding-related acute complications all presented at the time of RMB completion. The four subacute complications occurred from 28 hours to 18 days after RMB. Patients with, versus those without, a bleeding-related complication had a lower platelet count (mean, 197.7 vs 250.4 × 109/L, p = .01) and greater frequency of entirely endophytic renal masses (47.4% vs 19.6%, p = .01). CONCLUSION. Complications after RMB were uncommon and presented either within 3 hours after biopsy or more than 24 hours after biopsy. CLINICAL IMPACT. A 3-hour monitoring window after RMB before patient discharge (in the absence of deviation from normal clinical management and complemented by informing patients of the low risk of a subacute complication) may provide both safe patient management and appropriate resource utilization.

Detection of Local Cancer Recurrence After Stereotactic Ablative Radiation Therapy for Lung Cancer: Physician Performance Versus Radiomic Assessment.

PURPOSE: Stereotactic ablative radiation therapy (SABR) is a guideline-specified treatment option for early-stage lung cancer. However, significant posttreatment fibrosis can occur and obfuscate the detection of local recurrence. The goal of this study was to assess physician ability to detect timely local recurrence and to compare physician performance with a radiomics tool. METHODS AND MATERIALS: Posttreatment computed tomography (CT) scans (n=182) from 45 patients treated with SABR (15 with local recurrence matched to 30 with no local recurrence) were used to measure physician and radiomic performance in assessing response. Scans were individually scored by 3 thoracic radiation oncologists and 3 thoracic radiologists, all of whom were blinded to clinical outcomes. Radiomic features were extracted from the same images. Performances of the physician assessors and the radiomics signature were compared. RESULTS: When taking into account all CT scans during the whole follow-up period, median sensitivity for physician assessment of local recurrence was 83% (range, 67%-100%), and specificity was 75% (range, 67%-87%), with only moderate interobserver agreement (κ = 0.54) and a median time to detection of recurrence of 15.5 months. When determining the early prediction of recurrence within <6 months after SABR, physicians assessed the majority of images as benign injury/no recurrence, with a mean error of 35%, false positive rate (FPR) of 1%, and false negative rate (FNR) of 99%. At the same time point, a radiomic signature consisting of 5 image-appearance features demonstrated excellent discrimination, with an area under the receiver operating characteristic curve of 0.85, classification error of 24%, FPR of 24%, and FNR of 23%. CONCLUSIONS: These results suggest that radiomics can detect early changes associated with local recurrence that are not typically considered by physicians. This decision support system could potentially allow for early salvage therapy of patients with local recurrence after SABR.

Free-breathing pulmonary 1H and Hyperpolarized 3He MRI: comparison in COPD and bronchiectasis.

RATIONALE AND OBJECTIVES: In this proof-of-concept demonstration, we aimed to quantitatively and qualitatively compare pulmonary ventilation abnormalities derived from Fourier decomposition of free-breathing (1)H magnetic resonance imaging (FDMRI) to hyperpolarized (3)He MRI in subjects with chronic obstructive pulmonary disease (COPD) and bronchiectasis. MATERIALS AND METHODS: All subjects provided written informed consent to a protocol approved by a local research ethics board and Health, Canada, and they underwent MRI, computed tomography (CT), spirometry, and plethysmography during a single 2-hour visit. Semiautomated segmentation was used to generate ventilation defect measurements derived from FDMRI and (3)He MRI, and these were compared using analysis of variance and Pearson correlations. RESULTS: Twenty-six subjects were evaluated including 12 COPD subjects (67 ± 9 years) and 14 bronchiectasis subjects (70 ± 11 years). For COPD subjects, FDMRI and (3)He MRI ventilation defect percent (VDP) was 7 ± 6% and 24 ± 14%, respectively (P < .001; bias = -16 ± 9%). In COPD subjects, FDMRI was significantly correlated with (3)He MRI VDP (r = .88; P = .0001), (3)He MRI apparent diffusion coefficient (r = .71; P < .05), airways resistance (r = .60; P < .05), and RA950 (r = .80; P < .01). In subjects with bronchiectasis, FDMRI VDP (5 ± 3%) and (3)He MRI VDP (18 ± 9%) were significantly different (P < .001) and not correlated (P > .05). The Dice similarity coefficient (DSC) for FDMRI and (3)He MRI ventilation was 86 ± 7% for COPD and 86 ± 4% for bronchiectasis subjects (P > .05); the DSC for FDMRI ventilation defects and CT RA950 was 19 ± 20% in COPD and 2 ± 3% in bronchiectasis subjects (P < .01). CONCLUSIONS: FDMRI and (3)He MRI VDP were strongly related in COPD but not in bronchiectasis subjects. In COPD only, FDMRI ventilation defects were spatially related with (3)He ventilation defects and emphysema.

Ultra-short echo-time pulmonary MRI: evaluation and reproducibility in COPD subjects with and without bronchiectasis.

BACKGROUND: To evaluate ultra-short-echo-time (UTE) MRI pulmonary signal-intensity measurements and reproducibility in chronic obstructive pulmonary disease (COPD). METHODS: A two-dimensional sequence (echo-time = 0.05 ms; acquisition-time = 13 s) with interleaved half-pulse excitation and radial ramp-sampling was used with compressed-sensing to reconstruct UTE images from under-sampled data. Five healthy volunteers and 15 subjects with COPD provided written informed consent to imaging and pulmonary-function-tests. Healthy volunteers underwent MRI at four lung volumes: full-expiration, functional-residual-capacity (FRC), FRC+1L, and full-inhalation; COPD patients underwent computed-tomography (CT) and MRI at FRC+1L. Three-week reproducibility was evaluated and the relative area of the density histogram ≤ -950 HU (RA950 ) was compared with mean MRI signal-intensity. The 15th percentile of signal-intensity-histogram (SI15 ) was compared with the 15th percentile of the CT-density-histogram (HU15 ). RESULTS: In healthy subjects, signal-intensity correlated with the inverse of lung volume (r = 0.99; P = 0.007). Contrast-to-noise and signal-to-noise ratios were significantly improved for 32-channel UTE (P < 0.01). The coefficient of variation for 3-week repeated measurements was 4%. There were significant correlations for signal-intensity with RA950 (r = -0.71; P = 0.005), FEV1 /FVC (r = 0.59; P = 0.02), and for SI15 with HU15 (r = 0.62; P = 0.01). CONCLUSION: Pulmonary signal-intensity is reproducible and related to tissue density. In COPD subjects with and without bronchiectasis, signal-intensity was also related to pulmonary function and CT measurements.

Hyperpolarized 3He and 129Xe magnetic resonance imaging apparent diffusion coefficients: physiological relevance in older never- and ex-smokers.

Noble gas pulmonary magnetic resonance imaging (MRI) is transitioning away from (3)He to (129)Xe gas, but the physiological/clinical relevance of (129)Xe apparent diffusion coefficient (ADC) parenchyma measurements is not well understood. Therefore, our objective was to generate (129)Xe MRI ADC for comparison with (3)He ADC and with well-established measurements of alveolar structure and function in older never-smokers and ex-smokers with chronic obstructive pulmonary disease (COPD). In four never-smokers and 10 COPD ex-smokers, (3)He (b = 1.6 sec/cm(2)) and (129)Xe (b = 12, 20, and 30 sec/cm(2)) ADC, computed tomography (CT) density-threshold measurements, and the diffusing capacity for carbon monoxide (DLCO) were measured. To understand regional differences, the anterior-posterior (APG) and superior-inferior (∆SI) ADC differences were evaluated. Compared to never-smokers, COPD ex-smokers showed greater (3)He ADC (P = 0.006), (129)Xe ADCb12 (P = 0.006), and ADCb20 (P = 0.006), but not for ADCb30 (P > 0.05). Never-smokers and COPD ex-smokers had significantly different APG for (3)He ADC (P = 0.02), (129)Xe ADCb12 (P = 0.006), and ADCb20 (P = 0.01), but not for ADCb30 (P > 0.05). ∆SI for never- and ex-smokers was significantly different for (3)He ADC (P = 0.046), but not for (129)Xe ADC (P > 0.05). There were strong correlations for DLCO with (3)He ADC and (129)Xe ADCb12 (both r = -0.95, P < 0.05); in a multivariate model (129)Xe ADCb12 was the only significant predictor of DLCO (P = 0.049). For COPD ex-smokers, CT relative area <-950 HU (RA950) correlated with (3)He ADC (r = 0.90, P = 0.008) and (129)Xe ADCb12 (r = 0.85, P = 0.03). In conclusion, while (129)Xe ADCb30 may be appropriate for evaluating subclinical or mild emphysema, in this small group of never-smokers and ex-smokers with moderate-to-severe emphysema, (129)Xe ADCb12 provided a physiologically appropriate estimate of gas exchange abnormalities and alveolar microstructure.

Semi-automated scoring of pulmonary emphysema from X-ray CT: trainee reproducibility and accuracy.

OBJECTIVE: We developed a semi-automated tool to quantify emphysema from thoracic X-ray multi-detector (64-slice) computed tomography (CT) for training purposes and multi-reader studies. MATERIALS AND METHODS: Thoracic X-ray CT was acquired in 93 ex-smokers, who were evaluated by six trainees with little or no expertise (trainees) and a single experienced thoracic radiologist (expert). A graphic user interface (GUI) was developed for emphysema quantification based on the percentile of lung where a score of 0=no abnormalities, 1=1-25%, 2=26-50%, 3=51-75% and 4=76-100% for each lung side/slice. Trainees blinded to subject characteristics scored randomized images twice; accuracy was determined by comparison to expert scores, density histogram 15th percentile (HU 15), relative area at -950 HU (RA(950)), low attenuation clusters at -950 HU (LAC(950)), -856 HU (LAC(856)) and the diffusing capacity for carbon monoxide (DL(CO%pred)). Intra- and inter-observer reproducibility was evaluated using coefficients-of-variation (COV), intra-class (ICC) and Pearson correlations. RESULTS: Trainee-expert correlations were significant (r=0.85-0.97, p<0.0001) and a significant trainee bias (0.15 ± 0.22) was observed. Emphysema score was correlated with RA(950) (r=0.88, p<0.0001), HU 15 (r=-0.77, p<0.0001), LAC(950) (r=0.76, p<0.0001), LAC(856) (r=0.74, p=0.0001) and DLCO%pred (r=-0.71, p<0.0001). Intra-observer reproducibility (COV=4-27%; ICC=0.75-0.94) was moderate to high for trainees; intra- and inter-observer COV were negatively and non-linearly correlated with emphysema score. CONCLUSION: We developed a GUI for rapid and interactive emphysema scoring that allows for comparison of multiple readers with clinical and radiological standards.

Computed tomography density histogram analysis to evaluate pulmonary emphysema in ex-smokers.

RATIONALE AND OBJECTIVES: High-resolution computed tomography (CT) measurements of emphysema typically use Hounsfield unit (HU) density histogram thresholds or observer scores based on regions of low x-ray attenuation. Our objective was to develop an automated measurement of emphysema using principal component analysis (PCA) of the CT density histogram. MATERIALS AND METHODS: Ninety-seven ex-smokers, including 53 subjects with chronic obstructive pulmonary disease (COPD) and 44 asymptomatic subjects (AEs), provided written informed consent to imaging as well as plethysmography and spirometry. We applied PCA to the CT density histogram to generate whole lung and regional density histogram principal components including the first and second components and the sum of both principal components (density histogram principal component score [DHPCS]). Significant relationships for DHPCS with single HU thresholds, pulmonary function measurements, an expert's emphysema score, and hyperpolarized (3)He magnetic resonance imaging apparent diffusion coefficients (ADCs) were determined using linear regression and Pearson coefficients. Receiver operator characteristics analysis was performed using forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) as the independent diagnostic. RESULTS: There was a significant difference (P < .0001) between AE and COPD subjects for DHPCS; FEV1/FVC; diffusing capacity of lung for carbon monoxide%predicted; attenuation values below -950, -910, and -856 HU; and (3)He ADCs. There were significant correlations for DHPCS with FEV1/FVC (r = -0.85, P < .0001); diffusing capacity of lung for carbon monoxide%predicted (r = -0.67, P < .0001); attenuation values below -950/-910/-856 HU (r = 0.93/0.96/0.76, P < .0001); and (3)He ADCs (r = 0.85, P < .0001). Receiver operator characteristics analysis showed a 91% classification rate for DHPCS. CONCLUSIONS: We generated an automated emphysema score using PCA of the CT density histogram with a 91% COPD classification rate that showed strong and significant correlations with pulmonary function tests, single HU thresholds, and (3)He magnetic resonance imaging ADCs.

Hyperpolarized helium-3 magnetic resonance imaging of chronic obstructive pulmonary disease exacerbation.

A chronic obstructive pulmonary disease (COPD) exsmoker underwent pulmonary function tests and hyperpolarized helium-3 ((3) He) magnetic resonance imaging (MRI) serially over 4 years, twice prior to and twice following an acute exacerbation (AE). About 2.5 years pre-AE, (3) He ventilation defect percent (VDP) was 16%, the apparent diffusion coefficient (ADC) was 0.34 cm(2) /s, and forced expiratory volume in 1 sec (FEV1 ) was 41%pred . Six months pre-AE, VDP and ADC were worse (29% and 0.38 cm(2) /s, respectively) without worsening FEV1 (47%pred ). After hospitalization and AE treatment, VDP was 20%, whereas FEV1 did not improve (45%pred ); 16 months post-AE, both VDP and ADC remained improved and similar to 4 years prior.

Hyperpolarized 3He and 129Xe MR imaging in healthy volunteers and patients with chronic obstructive pulmonary disease.

PURPOSE: To quantitatively compare hyperpolarized helium 3 (3He) and xenon 129 (129Xe) magnetic resonance (MR) images obtained within 5 minutes in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD) and to evaluate the correlations between 3He and 129Xe MR imaging measurements and those from spirometry and plethysmography. MATERIALS AND METHODS: This study was approved by an ethics board and compliant with HIPAA. Written informed consent was obtained from all subjects. Eight healthy volunteers and 10 patients with COPD underwent MR imaging, spirometry, and plethysmography. Ventilation defect percentages (VDPs) at 3He and 129Xe imaging were obtained by using semiautomated segmentation. Apparent diffusion coefficients (ADCs) were calculated from 3He (b=1.6 sec/cm2) and 129Xe (b=12 sec/cm2) diffusion-weighted images. VDPs at hyperpolarized 3He and 129Xe imaging were compared with a two-tailed Wilcoxon signed rank test and analysis of variance; Pearson correlation coefficients were used to evaluate the relationships among measurements. RESULTS: 129Xe VDP was significantly greater than 3He VDP for patients with COPD (P<.0001) but not for healthy volunteers (P=.35), although 3He and 129Xe VDPs showed a significant correlation for all subjects (r=0.91, P<.0001). The forced expiratory volume in 1 second (FEV1) showed a similar and significant correlation with 3He VDP (r=-0.84, P<.0001) and 129Xe VDP (r=-0.89, P<.0001), although the correlation between the FEV1/forced vital capacity (FVC) ratio and 129Xe VDP (r=-0.95, P<.0001) was significantly greater (P=.01) than that for FEV1/FVC and 3He VDP (r=-0.84, P<.0001). A significant correlation was also observed for 3He and 129Xe ADC (r=0.97, P<.0001); 129Xe ADC was significantly correlated with diffusing capacity of lung for carbon monoxide (r=-0.79, P=.03) and computed tomographic emphysema measurements (areas with attenuation values in the 15th percentile: r=-0.91, P=.0003; relative areas with attenuation values of less than -950 HU: r=0.87, P=.001). CONCLUSION: In patients with COPD, the VDP obtained with hyperpolarized 29Xe MR imaging was significantly greater than that with 3He MR imaging, suggesting incomplete or delayed filling of lung regions that may be related to the different properties of 129Xe gas and physiologic and/or anatomic abnormalities in COPD.

Hyperpolarized (3)He pulmonary functional magnetic resonance imaging prior to radiation therapy.

PURPOSE: Radiation-induced lung injury (RILI) is the primary dose-limiting toxicity for radiation therapy of the lung, and although the effects of radiation dose on RILI development have been well characterized, the influence of chronic obstructive pulmonary disease (COPD) on the development of RILI and other outcomes is not well understood. The purpose of this small pilot study was to evaluate the relationship between hyperpolarized (3)He magnetic resonance imaging (MRI) measurements of COPD with RILI and 12-month survival in lung cancer patients undergoing radical radiotherapy and to evaluate the feasibility of pulmonary functional MRI as an image guidance∕planning tool for radiation therapy. METHODS: Fifteen non-small cell and small cell lung cancer patients underwent pulmonary function tests, x-ray computed tomography (CT), and hyperpolarized (3)He MRI prior to radical radiation therapy (≥60 Gy). Conventional thoracic (1)H and hyperpolarized (3)He MRI were acquired to generate ventilation defect percent and the apparent diffusion coefficient for the ipsilateral and contralateral lungs independently. CT was acquired postradiation therapy and qualitatively evaluated for radiological evidence of RILI and 12-month survival was reported. RESULTS: Hyperpolarized (3)He MRI measurements of COPD classified 10∕15 subjects with contralateral lung COPD (CLC), and five subjects without COPD [contralateral lung normal (CLN)]. Of the 10 subjects with CLC, only four had a previous clinical diagnosis of COPD. CT images were acquired postradiation therapy for 13 subjects, and for eight (62%) of these there was qualitative evidence of RILI, including 5∕9 CLC and 3∕4 CLN subjects. The one-year survival was 2∕10 for CLC and 3∕5 for CLN subjects. CONCLUSIONS: In this small pilot study, we report the use of (3)He MRI to stratify lung cancer patients based on MRI evidence of COPD and showed that comorbid COPD was present in the majority of lung cancer subjects stratified for radiation therapy. Lung cancer patients with imaging evidence of COPD did not have an increased incidence of RILI compared to patients without COPD. However, preliminary data presented here indicated that one-year survival in COPD subjects was lower than expected based on previously published survival rates, which may have implications for radiation therapy in lung cancer patients with comorbid COPD.

Hyperpolarized 3He functional magnetic resonance imaging of bronchoscopic airway bypass in chronic obstructive pulmonary disease.

A 73-year-old exsmoker with Global initiative for chronic Obstructive Lung Disease stage III chronic obstructive pulmonary disease underwent airway bypass (AB) as part of the Exhale Airway Stents for Emphysema (EASE) trial, and was the only EASE subject to undergo hyperpolarized 3He magnetic resonance imaging for evaluation of lung function pre- and post-AB. 3He magnetic resonance imaging was acquired twice previously (32 and eight months pre-AB) and twice post-AB (six and 12 months post-AB). Six months post-AB, his increase in forced vital capacity was <12% predicted, and he was classified as an AB nonresponder. However, post-AB, he also demonstrated improvements in quality of life scores, 6 min walk distance and improvements in 3He gas distribution in the regions of stent placement. Given the complex relationship between well-established pulmonary function and quality of life measurements, the present case provides evidence of the value-added information functional imaging may provide in chronic obstructive pulmonary disease interventional studies.

Hyperpolarized 3He magnetic resonance functional imaging semiautomated segmentation.

RATIONALE AND OBJECTIVES: To improve intra- and interobserver variability and enable the use of functional magnetic resonance imaging (MRI) for multicenter, multiobserver studies, we generated a semiautomated segmentation method for hyperpolarized helium-3 ((3)He) MRI. Therefore the objective of this study was to compare the reproducibility and spatial agreement of manual and semiautomated segmentation of (3)He MRI ventilation defect volume (VDV) and ventilation volume (VV) in subjects with asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). MATERIALS AND METHODS: The multistep semiautomated segmentation method we developed employed hierarchical K-means clustering to classify (3)He MRI pixel intensity values into five user-determined clusters ranging from signal void to hyperintense. A seeded region-growing algorithm was also used to segment the (1)H MRI thoracic cavity for coregistration to the (3)He cluster-map, generating VDV and VV. RESULTS: We compared manual segmentation performed by an expert observer and semiautomated measurements of (3)He MRI VDV and observed strong significant correlations between the volumes generated using each method (asthma, n = 5, r = 0.89, P < .0001; COPD, n = 5, r = 0.84, P < .0001; CF, n = 5, r = 0.89, P < .0001). Semiautomated VDV had high interobserver reproducibility (coefficient of variation [CV] = 7%, intraclass correlation coefficient [ICC] = 0.96); intraobserver reproducibility was significantly higher for semiautomated (CV = 5%, ICC = 1.00) compared to manual VDV (CV = 12%, ICC = 0.98). Spatial agreement for VV determined using the Dice coefficient (D) was also high for all disease states (asthma, D = 0.95; COPD, D = 0.88; CF, D = 0.90). CONCLUSIONS: Semiautomated segmentation (3)He MRI provides excellent inter- and intraobserver precision with high spatial and quantitative agreement with manual measurements enabling its use in longitudinal studies.

Pulmonary tumor measurements from x-ray computed tomography in one, two, and three dimensions.

RATIONALE AND OBJECTIVES: We evaluated the accuracy and reproducibility of three-dimensional (3D) measurements of lung phantoms and patient tumors from x-ray computed tomography (CT) and compared these to one-dimensional (1D) and two-dimensional (2D) measurements. MATERIALS AND METHODS: CT images of three spherical and three irregularly shaped tumor phantoms were evaluated by three observers who performed five repeated measurements. Additionally, three observers manually segmented 29 patient lung tumors five times each. Follow-up imaging was performed for 23 tumors and response criteria were compared. For a single subject, imaging was performed on nine occasions over 2 years to evaluate multidimensional tumor response. To evaluate measurement accuracy, we compared imaging measurements to ground truth using analysis of variance. For estimates of precision, intraobserver and interobserver coefficients of variation and intraclass correlations (ICC) were used. Linear regression and Pearson correlations were used to evaluate agreement and tumor response was descriptively compared. RESULTS: For spherical shaped phantoms, all measurements were highly accurate, but for irregularly shaped phantoms, only 3D measurements were in high agreement with ground truth measurements. All phantom and patient measurements showed high intra- and interobserver reproducibility (ICC >0.900). Over a 2-year period for a single patient, there was disagreement between tumor response classifications based on 3D measurements and those generated using 1D and 2D measurements. CONCLUSION: Tumor volume measurements were highly reproducible and accurate for irregular, spherical phantoms and patient tumors with nonuniform dimensions. Response classifications obtained from multidimensional measurements suggest that 3D measurements provide higher sensitivity to tumor response.

Chronic obstructive pulmonary disease: quantification of bronchodilator effects by using hyperpolarized ³He MR imaging.

PURPOSE: To evaluate short-acting bronchodilator effects in chronic obstructive pulmonary disease (COPD) by using hyperpolarized helium 3 (³He) magnetic resonance (MR) imaging, spirometry, and plethysmography. MATERIALS AND METHODS: Fourteen ex-smokers with COPD provided written informed consent to a local ethics board-approved and Health Insurance and Portability Accountability Act-compliant protocol and underwent hyperpolarized ³He and hydrogen 1 MR imaging, spirometry, and plethysmography before and a mean of 25 minutes ± 2 (standard deviation) after administration of 400 µg salbutamol. Distribution of ³He gas was evaluated by using semiautomated segmentation of ³He voxel intensities, where cluster 1 represented regions of signal void or ventilation defect volume (VDV), and clusters 2-5 (C2-C5) represented gradations of signal intensity from hypointensity (C2) to hyperintensity (C5). ³He ventilation defect percentage (VDP) was calculated as VDV normalized to the thoracic cavity volume. Comparisons of pre- and post-salbutamol means were performed by using a two-way mixed-design repeated measures analysis of variance, and comparisons of the magnitude of the treatment effect between pulmonary function and ³He MR imaging measurements were performed by using effect size (ES) calculations. The relationships between pulmonary function and ³He MR imaging findings were determined by using Spearman correlation coefficients. RESULTS: After salbutamol administration, there were significant changes in forced expiratory volume in 1 second (FEV1) (P = .001), total lung capacity (P = .04), and functional residual capacity (P = .03), as well as VDP (P < .0001) and ³He gas distribution (C2, P = .01; C3, P = .03; C4, P < .0001; and C5, P = .02). Treatment ES was greater for ³He VDP than for FEV(1) (0.50 vs 0.22). There was a significant correlation between baseline VDP and post-salbutamol FEV1 change (r = -0.77, P = .001). Although five patients were classified as bronchodilator responders and nine patients were classified as bronchodilator nonresponders according to American Thoracic Society and European Respiratory Society criteria, there was no significant difference in the magnitude of the ³He MR imaging changes after salbutamol administration between responder groups. CONCLUSION: ³He MR imaging depicted significant improvements in the distribution of ³He gas after bronchodilator therapy in ex-smokers with COPD with and those without clinically important changes in FEV1.

Quantitative evaluation of hyperpolarized helium-3 magnetic resonance imaging of lung function variability in cystic fibrosis.

RATIONALE AND OBJECTIVES: To better understand imaging measurement precision and reproducibility and to provide guidance for measurements in individual cystic fibrosis (CF) subjects, we evaluated CF adults on two occasions 7 ± 2 days apart using spirometry, plethysmography, and hyperpolarized helium-3 ((3)He) magnetic resonance imaging (MRI). MATERIALS AND METHODS: Twelve CF subjects underwent spirometry, plethysmography, and (3)He MRI twice within 7 ± 2 days, reporting (3)He ventilation defect volume (VDV) and ventilation defect percent (VDP). RESULTS: Based on measurement variability, the smallest detectable difference (SDD) for (3)He VDV and VDP was determined to be 120 mL and 2%, respectively. Although no significant difference in spirometry or plethysmography was detected after 7 days, there was a significant difference in mean (3)He VDV (130 mL ± 250 mL, P < .0001) and VDP (3% ± 4%, P < .0001), although baseline and 7-day measurements were highly correlated (VDV: r = .85, P = .001; VDP: r = .94, P < .0001). We estimated the sample sizes required to detect a 5%/7%/10% change in (3)He VDP as 60/15/5 subjects per group. CONCLUSION: Hyperpolarized (3)He MRI VDP measurement precision resulted in an SDD for individual CF subjects of 2%, indicating that changes greater than this can be attributed to lung functional changes and not measurement error. After 7 days, significant changes in mean (3)He VDV and VDP were detected and these changes were not reflected by changes in pulmonary function measurements. These findings demonstrate the high sensitivity and reproducibility of (3)He MRI functional imaging that permits the use of relatively small samples sizes in CF interventional studies.

Hyperpolarized ³He magnetic resonance imaging: preliminary evaluation of phenotyping potential in chronic obstructive pulmonary disease.

RATIONALE AND OBJECTIVES: Emphysema and small airway obstruction are the pathological hallmarks of chronic obstructive pulmonary disease (COPD). The aim of this pilot study in a small group of chronic obstructive pulmonary disease (COPD) patients was to quantify hyperpolarized helium-3 ((3)He) magnetic resonance imaging (MRI) functional and structural measurements and to explore the potential role for (3)He MRI in detecting the lung structural and functional COPD phenotypes. MATERIALS AND METHODS: We evaluated 20 ex-smokers with stage I (n=1), stage II (n=9) and stage III COPD (n=10). All subjects underwent same-day plethysmography, spirometry, (1)H MRI and hyperpolarized (3)He MRI at 3.0T. (3)He ventilation defect percent (VDP) was generated from (3)He static ventilation images and (1)H thoracic images and the (3)He apparent diffusion coefficient (ADC) was derived from diffusion-weighted MRI. RESULTS: Based on the relative contribution of normalized ADC and VDP, there was evidence of a predominant (3)He MRI measurement in seven patients (n=3 mainly ventilation defects or VDP dominant (VD), n=4 mainly increased ADC or ADC dominant (AD)). Analysis of variance (ANOVA) showed significantly lower ADC for subjects with predominantly elevated VDP (p=0.02 compared to subjects with predominantly elevated ADC; p=0.008 compared to mixed group) and significantly decreased VDP for subjects with predominantly elevated ADC (p=0.003, compared to mixed group). CONCLUSION: In this small pilot study, a preliminary analysis shows the potential for (3)He MRI to categorize or phenotype COPD ex-smokers, providing good evidence of feasibility for larger prospective studies.

Detection of longitudinal lung structural and functional changes after diagnosis of radiation-induced lung injury using hyperpolarized 3He magnetic resonance imaging.

PURPOSE: Therapeutic radiation doses for thoracic tumors are significantly restricted to decrease the risk of nontumor tissue damage, yet radiation-induced lung injury (RILI) still occurs in over 1/3 of thoracic radiation treatment cases. Although RILI can be clinically monitored using pulmonary function measurements, the regional functional effects of the injury are not well understood. Hyperpolarized 3He magnetic resonance imaging provides measurements of regional lung function and structure with high spatial and temporal resolution; the authors use this tool longitudinally for the first time in seven subjects after clinical diagnosis of RILI in order to better understand regional changes in lung function and structure post-RILI. METHODS: All subjects underwent spirometry, plethysmography, and MRI at 3.0 T 35.1 +/- 12.2 weeks after radiation therapy commenced. Thoracic 1H, static 3He ventilation, and 3He diffusion-weighted images were acquired to generate the 3He apparent diffusion coefficient (ADC) and 3He percent ventilated volume (PVV). Four subjects returned 22.0 +/- 0.8 weeks after baseline imaging for follow-up spirometry and 3He MRI measurements of ADC and PVV. RESULTS: At baseline, PVV was significantly different (p = 0.025) and lower in the ipsilateral diseased lung (55 +/- 29%) compared to the contralateral nondiseased lung (88 +/- 5%). Longitudinally, significant increases were observed for 3He MRI PVV (16% +/- 6%, p = 0.012) and 3He MRI ADC (0.02 +/- 0.01 cm2/s, p = 0.003) in the contralateral lung only, in the four subjects who returned for follow-up, while no changes in the ipsilateral lung were reported. CONCLUSIONS: Hyperpolarized 3He MRI was well tolerated in all subjects with moderate to severe RILI. Functional improvements and microstructural changes were observed in the contralateral lung, while the ipsilateral lung remained stable, suggesting that functional compensatory changes may have occurred in the contralateral lung due to ipsilateral lung radiation-induced injury.