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Rationale and Objectives Phase resolved functional lung (PREFUL) magnetic resonance imaging (MRI) is a free-breathing 1H-based technique that produces maps of fractional ventilation (FV). This study compared ventilation defect percent (VDP) calculated using PREFUL to hyperpolarized (HP) 129Xe MRI and pulmonary function tests in pediatric cystic fibrosis (CF). Materials and Methods 27 pediatric participants were recruited (mean age 13.0 ± 2.7), including 6 with clinically stable CF, 11 CF patients undergoing a pulmonary exacerbation (PEx), and 10 healthy controls. Spirometry was performed to measure forced expiratory volume in 1 second (FEV1), along with nitrogen multiple breath washout to measure lung clearance index (LCI). VDP was calculated from single central coronal slice PREFUL FV maps and the corresponding HP 129Xe slice. Results The stable CF group had a normal FEV1 (p = 0.41) and elevated LCI (p = 0.007). The CF PEx group had a decreased FEV1 (p Conclusion PREFUL MRI is feasible in pediatric CF, distinguishes patients undergoing pulmonary exacerbations compared to healthy subjects, and correlates with HP 129Xe MRI as well as functional measures of disease severity. PREFUL MRI does not require breath-holds and is straight forward to implement on any MRI scanner.

Conventional pulmonary function tests appear normal in early cystic fibrosis (CF) lung disease. Therefore, new diagnostic approaches are required that can detect CF lung disease in children and monitor treatment response. Hyperpolarized (HP) gas (129Xe and 3He) magnetic resonance imaging (MRI) is a powerful, emergent tool for mapping regional lung function and may be well suited for studying pediatric CF. HP gas MRI is well tolerated, reproducible, and it can be performed longitudinally without the need for ionizing radiation. In particular, quantification of the distribution of ventilation, or ventilation defect percent (VDP), has been shown to be a sensitive indicator of CF lung disease and correlates well with pulmonary function tests. This article presents the current state of CF diagnosis and treatment and describes the potential role of HP gas MRI for detection of early CF lung disease and following the effects of interventions. The typical HP gas imaging workflow is described, along with a discussion of image analysis to calculate VDP, dosing considerations, and the reproducibility of VDP. The potential use of VDP as an outcome measure in CF is discussed, by considering the correlation with pulmonary function measures, preliminary interventional studies, and case studies involving longitudinal imaging and pulmonary exacerbations. Finally, emerging HP gas imaging techniques such as multiple breath washout imaging are introduced, followed by a discussion of future directions. Overall, HP gas MRI biomarkers are expected to provide sensitive outcome measures that can be used in disease surveillance as well as interventional studies involving novel CF therapies.

Rationale and Objectives The objective of this study was to evaluate the tolerability of hyperpolarized 129 Xe gas inhaled from functional residual capacity and magnetic resonance imaging in healthy subjects and those with pulmonary disease. Materials and Methods Twelve healthy volunteers (mean age, 59 ± 17 years), seven subjects with asthma (mean age, 47 ± 7 years), 10 subjects with chronic obstructive pulmonary disease (mean age, 74 ± 4 years), three subjects with cystic fibrosis (mean age, 27 ± 10 years), and a single subject with radiation-induced lung injury (age, 66 years) were enrolled and evaluated over 43 visits with 136 anoxic inhalations of 500 mL 129 Xe gas mixed with 500 mL 4 He gas. Oxygen saturation and heart rate were monitored during the breath-hold and imaging; subjects were queried for adverse events (AEs) before and immediately following gas inhalation and for 24 hours after the last dose. Results No subjects withdrew from the study or reported serious, hypoxic, or severe AEs. Over the course of 136 dose administrations, two mild AEs (1%) were reported in two different subjects (two of 33 [6%]). One of these AEs (light-headedness) was temporally related and judged as possibly related to 129 Xe administration and resolved without treatment within 2 minutes. Statistically significant but clinically insignificant changes in oxygen saturation and heart rate were observed after inhalation ( P Conclusions Inhalation of hyperpolarized 129 Xe gas and subsequent magnetic resonance imaging were well tolerated in healthy subjects and ambulatory subjects with obstructive and restrictive pulmonary disease.

Rationale and Objectives We assessed subjects with stage II and stage III chronic obstructive pulmonary disease (COPD) and age-matched healthy volunteers at a single center using 3He magnetic resonance imaging (MRI) at 3.0 T. Measurements of the 3He apparent diffusion coefficient (ADC) and center coronal slice 3He ventilation defect volume (VDV) were examined for same-day and 7-day reproducibility as well as subgroup comparisons. Materials and Methods Twenty-four subjects who provided written informed consent (15 males; mean age 67 ±7 years) with stage II (n = 9), stage III COPD (n = 7), and age-matched healthy volunteers (n = 8) were enrolled based on their age and pulmonary function test results. All subjects underwent plethysmography, spirometry, and MRI at 3.0 T. The time frame between scans was 7 ± 2 minutes (same-day rescan) and again 7 ± 2 days later (7-day rescan). 3He ADC and VDV reproducibility was evaluated using linear regression, intraclass correlation coefficients (ICC) and Lin's concordance correlation coefficients (CCC). Results ADC reproducibility was high for same-day rescan (r2 = 0.934) and 7-day rescan (r2 = 0.960, ICC and CCC of 0.96 and 0.98, respectively). Same-day rescan VDV reproducibility evaluated using the ICC and CCC (0.97 and 0.98, respectively) as well as linear regression (r2 = 0.941) was also high, but VDV 7-day rescan reproducibility was lower and significantly different (r2 = 0.576, P Conclusions Hyperpolarized 3He MRI was well-tolerated in subjects with stage II and stage III COPD. Seven-day repeated scanning was highly reproducible for ADC and moderately reproducible for VDV.

Rationale and Objectives Hyperpolarized 3 He magnetic resonance imaging ventilation defects have been observed in subjects with respiratory disorders. We quantified 3 He ventilation defects in elderly and middle-aged subjects who had no history of smoking, respiratory, or cardiovascular disorders. Materials and Methods Hyperpolarized 3 He magnetic resonance imaging ventilation defect volume (VDV) and ventilation defect score (VDS) were assessed in eight elderly healthy volunteers (mean 67 ± 6 years) scanned twice within 7 ± 2 minutes and again 7 ± 2 days later. A younger cohort of 24 subjects (mean 44 ± 10 years) was also scanned for direct comparison. Four observers blinded to scan timepoint and subject identity scored VDS and manually segmented VDV in all center coronal slices. Results Center coronal slice ventilation defects were observed in six of eight elderly subjects (ages 63–74 years, 5 males) in all scans acquired and in no middle-aged subjects. At the scan timepoint, mean VDS was 2.7 (mean VDV 52 ± 34 cm 3 ), whereas for same-day rescan, mean VDS was 2.5 (mean VDV 53 ± 35 cm 3 ) and at 7-day rescan, mean VDS was 3.6 (mean VDV 48 ± 39 cm 3 ). Interscan coefficients of variation (COV) for mean VDV was 1.8% (same-day rescan) and 5.3% (7-day rescan) and interobserver COV ranged from 10–12%. Conclusion Elderly subjects have ventilation defects that are reproducible in same-day scanning and 7-day scanning visits. The observation of reproducible pulmonary ventilation defects in otherwise healthy elderly volunteers suggests caution must be used in interpreting results from 3 He studies of elderly subjects.

The objective of this study was to evaluate the tolerability of hyperpolarized (129)Xe gas inhaled from functional residual capacity and magnetic resonance imaging in healthy subjects and those with pulmonary disease.Twelve healthy volunteers (mean age, 59 ± 17 years), seven subjects with asthma (mean age, 47 ± 7 years), 10 subjects with chronic obstructive pulmonary disease (mean age, 74 ± 4 years), three subjects with cystic fibrosis (mean age, 27 ± 10 years), and a single subject with radiation-induced lung injury (age, 66 years) were enrolled and evaluated over 43 visits with 136 anoxic inhalations of 500 mL (129)Xe gas mixed with 500 mL (4)He gas. Oxygen saturation and heart rate were monitored during the breath-hold and imaging; subjects were queried for adverse events (AEs) before and immediately following gas inhalation and for 24 hours after the last dose.No subjects withdrew from the study or reported serious, hypoxic, or severe AEs. Over the course of 136 dose administrations, two mild AEs (1%) were reported in two different subjects (two of 33 [6%]). One of these AEs (light-headedness) was temporally related and judged as possibly related to (129)Xe administration and resolved without treatment within 2 minutes. Statistically significant but clinically insignificant changes in oxygen saturation and heart rate were observed after inhalation (P.001), and both resolved 1 minute later, with no difference between subject groups.Inhalation of hyperpolarized (129)Xe gas and subsequent magnetic resonance imaging were well tolerated in healthy subjects and ambulatory subjects with obstructive and restrictive pulmonary disease.

Hyperpolarized (3)He magnetic resonance imaging ventilation defects have been observed in subjects with respiratory disorders. We quantified (3)He ventilation defects in elderly and middle-aged subjects who had no history of smoking, respiratory, or cardiovascular disorders.Hyperpolarized (3)He magnetic resonance imaging ventilation defect volume (VDV) and ventilation defect score (VDS) were assessed in eight elderly healthy volunteers (mean 67+/-6 years) scanned twice within 7+/-2 minutes and again 7+/-2 days later. A younger cohort of 24 subjects (mean 44+/-10 years) was also scanned for direct comparison. Four observers blinded to scan timepoint and subject identity scored VDS and manually segmented VDV in all center coronal slices.Center coronal slice ventilation defects were observed in six of eight elderly subjects (ages 63-74 years, 5 males) in all scans acquired and in no middle-aged subjects. At the scan timepoint, mean VDS was 2.7 (mean VDV 52+/-34 cm(3)), whereas for same-day rescan, mean VDS was 2.5 (mean VDV 53+/-35 cm(3)) and at 7-day rescan, mean VDS was 3.6 (mean VDV 48+/-39 cm(3)). Interscan coefficients of variation (COV) for mean VDV was 1.8% (same-day rescan) and 5.3% (7-day rescan) and interobserver COV ranged from 10-12%.Elderly subjects have ventilation defects that are reproducible in same-day scanning and 7-day scanning visits. The observation of reproducible pulmonary ventilation defects in otherwise healthy elderly volunteers suggests caution must be used in interpreting results from (3)He studies of elderly subjects.

2-4 An Algorithm for Incorporating Breast MRI into Clinical Practice Frederick Kelcz, Ph.D., M.D., Giles E. Santyr, Gregory O. Cron. University of Wisconsin. 2-5 Gadolinium Enhanced MRI of Core Biopsy Proven Fibroadenomas: Histologic Correlation Oliver Pomeroy, M.D., P. Mok, M.D., S. Lester, M.D., Ph.D., D. Adams, M.D., C. Tempany, M.D., F.A. Jolesz, M.D., Brigham & Women's Hospital. Purpose: We performed dynamic Gd-DTPA-enhanced breast MRI on 72 breast lesions to test an algorithm for using MR/to increase the currently low positive predictive value associated with mammographie biopsy. Methods: Dynamic Gd-anhanced breast MR/was performed at 1.5 T on 72 lesions using a dedicated breast coil. The results were classified according to a three step algorithm requiring answers to three questions: (a) Did the lesion enhance?; (b) Aider the initial enhancement was the trend toward increasing or decreasing signal intensity (SO?; and (c) What was the value of the normalized initial slope when the results were fit to a saturation equation? Results: The 72 lesions, all biopsy proven, consisted of 17 cancers, 16 fibroadenomas and 39 benign other lesions. All 26 non-enhancing lesions were benign; all cancers enhanced. 10 of 17 cancers displayed early washout, but only 2 of 2g benign lesions displayed this property. 16 of 17 benign lesions displayed a constant SI increase, a property displayed by only one malignant lesion. The normalized slope was, on the average, three times greater for malignant lesions than for benign lesions. Conclusion: Use of this three-step algorithm would have reduced the number of false negative biopsies from 55 to 5. The price paid is that 3 malignancies would have been misclassified as benign. Overall, MR/resulted in a sensitivity of 82% and a specificity of 91% in regard to breast malignancy. ~URPOSE TO correlate the MRI signal characteristics and enhancement features of breast fibroadenomas with their histologic patterns. M~TERIALS AICD~ODS 13 patients (14 lesions) with core biopsy proven fibroadenomas were imaged using the following pulse sequences; T x SE PRE and POST Gd, T 2 FSE, and dynamic Gd enhanced gradient echo imaging (FSPGR). MR features were correlated with the histologic patterns of stromal cellularity, collagen content, epithelial hyperplasia and number of vessels. RESULTS All lesions were identified on MRI. They ranged in size from 7mm to 3 cm. Ta weighted signal intensity ranged from high (7 cases), intermediates.(2) to low (5). 8 of 9 lesions with high/intermediate T 2 signal demonstrated moderate to marked enhancement with Gd (The Gd bolus in one patient infiltrated). 4 of 5 lesions with low T 2 signal demonstrated minimal to moderate enhancement (one lesion was only imaged on T 2) High/Intermediate T 2 signal correlated with myxoid stroma (8), epithelial hyperplasia (5) and mean number of vessels (mean 50 versus mean 25 for low T2). All lesions with marked gadolinium enhancement (3) had myxoid stroma, whereas the one lesion with minimal enhancement was densely collagenised. CONCLUSION We have demonstrated good correlation between histology and the expected MR signal characteristics, 3-1 Dynamic, Contrast-Enhanced CT and MRI of Focal Liver Lesions: Similarities, Differences and Explanations G. Scott Gazelle, M.D., Giles W. Boland, M.D., Michael J. Lee, M.D., Wiliam W. Mayo-Smith, M.D., Sanjay Saini, M.D., Peter R. Mueller, M.D. Massachusetts General Hospital. 3-2 A Molecular Receptor-Binding Contrast Agent for Magnetic Resonance Imaging of the Liver David R. Vera, Ph.D., Michael H. Buoncore, M.D, Ph.D., Erik R. Wisner, D.V.M., Richard W. Katzberg, M.D., Robert C. Stadalnik, M.D. University of California, Davis Medical Center. Purpose : To compare the enhancement patterns of focal liver lesions on dynamic contrastenhanced CT and MR/. Ma te r i a l s and M e t h o d s : Thirty patients with focal liver lesions underwent both CT and MR/immediately following intravenous contrast administration (diatrizoate or iohexol for CT; Gd-DTPA for MR/). Scans were performed within 2 minutes in all patients; additional delayed scans were performed in 15/30. Images were reviewed by 3 readers blinded to patient identity and lesion diagnosis; each independently recorded the enhancement pattern (none, homogeneous, heterogeneous, linear, single nodule, peripheral nodules, thin rim, thick rim) of each lesion. Readers viewed CT and MR images from each patient on different days; direct comparison was not permitted, lnter-modality and inter-reader variation were analyzed. ReslAlt$: Readers described similar enhancement patterns on CT and MR in 19/30, 17/30, and 14/30 cases (readers A, B, C). Readers agreed about CT enhancement patterns in 22/30 cases; at least 2/3 agreed in 28/30. Readers agreed about MRI enhancement patterns in 17/30 cases; at least 2/3 agreed in 28/30. C o n c l u s i o n : Though presumably representative of the same phenomena, enhancement patterns of liver lesions on CT and MR/using currently available contrast agents differ in up to 83% of patients. Potential explanations will be discussed. PUI'~OSE. A gadolinium complex of polydiethylanetriamian-pentancetie aeid-polyneogalactosylpolylysine (Gd-DTPA-gal-PL) was developed and tested as a paramagnetie contrast agent for magnetic resonance (MR) imaging of the liver. The agent was designed for receptor-mediated uptake by the asialogiycoprotein receptor (ASGP-R), which is unique to hepatoeytes and exhibits high specificity for galaetose-terrninated glyeoconjugates. METHODS. Polylysine was alkylated with a mixed anhydride of DTPA. This product was complexed with gadolinium, and N-alkylated with 3-oxopropyl-l-thio-p-D-galactopyranoside. With this reaction sequence, we prepared a gadolinium complex consisting of 2284 galaetose groups and 858 chelators per polylysine having 2I 36 amino groups. Hepatie enhancement was tested by MR imaging of (n=9) rats with liver-implanted mammary adenocarcinoma before and after injection of 20 0.1). The liver accumulated 90% ofthe Tc-99m-labeled conjugate. CONCLUSION. A molecular paramagnetic ligand to the asialogiycoprotein receptor has been developed for hepatocyte-specific MR contrast enhancement.