Highly accelerated dynamic acquisition of 3D grid-tagged hyperpolarized-gas lung images using compressed sensing.

PURPOSE: To develop and test compressed sensing-based multiframe 3D MRI of grid-tagged hyperpolarized gas in the lung. THEORY AND METHODS: Applying grid-tagging RF pulses to inhaled hyperpolarized gas results in images in which signal intensity is predictably and sparsely distributed. In the present work, this phenomenon was used to produce a sampling pattern in which k-space is undersampled by a factor of approximately seven, yet regions of high k-space energy remain densely sampled. Three healthy subjects received multiframe 3D 3 He tagging MRI using this undersampling method. Images were collected during a single exhalation at eight timepoints spanning the breathing cycle from end-of-inhalation to end-of-exhalation. Grid-tagged images were used to generate 3D displacement maps of the lung during exhalation, and time-resolved maps of principal strains and fractional volume change were generated from these displacement maps using finite-element analysis. RESULTS: Tags remained clearly resolvable for 4-6 timepoints (5-8 s) in each subject. Displacement maps revealed noteworthy temporal and spatial nonlinearities in lung motion during exhalation. Compressive normal strains occurred along all three principal directions but were primarily oriented in the head-foot direction. Fractional volume changes displayed clear bilateral symmetry, but with the lower lobes displaying slightly higher change than the upper lobes in 2 of the 3 subjects. CONCLUSION: We developed a compressed sensing-based method for multiframe 3D MRI of grid-tagged hyperpolarized gas in the lung during exhalation. This method successfully overcomes previous challenges for 3D dynamic grid-tagging, allowing time-resolved biomechanical readouts of lung function to be generated.

A hybrid proton and hyperpolarized gas tagging MRI technique for lung respiratory motion imaging: a feasibility study.

The aim of this work was to develop a novel hybrid 3D hyperpolarized (HP) gas tagging MRI (t-MRI) technique and to evaluate it for lung respiratory motion measurement with comparison to deformable image registrations (DIR) methods. Three healthy subjects underwent a hybrid MRI which combines 3D HP gas t-MRI with a low resolution (Low-R, 4.5 mm isotropic voxels) 3D proton MRI (p-MRI), plus a high resolution (High-R, 2.5 mm isotropic voxels) 3D p-MRI, during breath-holds at the end-of-inhalation (EOI) and the end-of-exhalation (EOE). Displacement vector field (DVF) of the lung motion was determined from the t-MRI images by tracking tagging grids and from the High-R p-MRI using three DIR methods (B-spline based method implemented by Velocity, Free Form Deformation by MIM, and B-spline by an open source software Elastix: denoted as A, B, and C, respectively), labeled as tDVF and dDVF, respectively. The tDVF from the HP gas t-MRI was used as ground-truth reference to evaluate performance of the three DIR methods. Differences in both magnitude and angle between the tDVF and dDVFs were analyzed. The mean lung motion of the three subjects was 37.3 mm, 8.9 mm and 12.9 mm, respectively. Relatively large discrepancies were observed between the tDVF and the dDVFs as compared to previously reported DIR errors. The mean ± standard deviation (SD) DVF magnitude difference was 8.3 ± 5.6 mm, 9.2 ± 4.5 mm, and 9.3 ± 6.1 mm, and the mean ± SD DVF angular difference was 29.1 ± 12.1°, 50.1 ± 28.6°, and 39.0 ± 6.3°, for the DIR Methods A, B, and C, respectively. These preliminary results showed that the hybrid HP gas t-MRI technique revealed different lung motion patterns as compared to the DIR methods. It may provide unique perspectives in developing and evaluating DIR of the lungs. Novelty and Significance We designed a MRI protocol that includes a novel hybrid MRI technique (3D HP gas t-MRI with a low resolution 3D p-MRI) plus a high resolution 3D p-MRI. We tested the novel hybrid MRI technique on three healthy subjects for measuring regional lung respiratory motion with comparison to deformable image registrations (DIR) methods, and observed relatively large discrepancies in lung motion between HP gas t-MRI and DIR methods.

An initial investigation of hyperpolarized gas tagging magnetic resonance imaging in evaluating deformable image registration-based lung ventilation.

BACKGROUND: Deformable image registration (DIR)-based lung ventilation mapping is attractive due to its simplicity, and also challenging due to its susceptibility to errors and uncertainties. In this study, we explored the use of 3D Hyperpolarized (HP) gas tagging MRI to evaluate DIR-based lung ventilation. METHOD AND MATERIAL: Three healthy volunteers included in this study underwent both 3D HP gas tagging MRI (t-MRI) and 3D proton MRI (p-MRI) using balanced steady-state free precession pulse sequence at end of inhalation and end of exhalation. We first obtained the reference displacement vector fields (DVFs) from the t-MRIs by tracking the motion of each tagging grid between the exhalation and the inhalation phases. Then, we determined DIR-based DVFs from the p-MRIs by registering the images at the two phases with two commercial DIR algorithms. Lung ventilations were calculated from both the reference DVFs and the DIR-based DVFs using the Jacobian method and then compared using cross correlation and mutual information. RESULTS: The DIR-based lung ventilations calculated using p-MRI varied considerably from the reference lung ventilations based on t-MRI among all three subjects. The lung ventilations generated using Velocity AI were preferable for the better spatial homogeneity and accuracy compared to the ones using MIM, with higher average cross correlation (0.328 vs 0.262) and larger average mutual information (0.528 vs 0.323). CONCLUSION: We demonstrated that different DIR algorithms resulted in different lung ventilation maps due to underlining differences in the DVFs. HP gas tagging MRI provides a unique platform for evaluating DIR-based lung ventilation.

Hyperpolarized helium-3 magnetic resonance lung imaging of non-sedated infants and young children: a proof-of-concept study.

PURPOSE: To develop and evaluate a protocol for hyperpolarized helium-3 (HHe) ventilation magnetic resonance imaging (MRI) of the lungs of non-sedated infants and children. MATERIALS AND METHODS: HHe ventilation MRI was performed on seven children ≤4years old. Contiguous 2D-spiral helium-3 images were acquired sequentially with a scan time of ≤0.2s/slice. RESULTS: Motion-artifact-free, high signal-to-noise ratio (SNR) images of lung ventilation were obtained. Gas was homogeneously distributed in healthy individuals; focal ventilation defects were found in patients with respiratory diseases. CONCLUSION: HHe ventilation MRI can aid assessment of pediatric lung disease even at a young age.

Hyperpolarized Helium-3 Diffusion-weighted Magnetic Resonance Imaging Detects Abnormalities of Lung Structure in Children With Bronchopulmonary Dysplasia.

PURPOSE: The aim of the study was to determine whether hyperpolarized He diffusion-weighted magnetic resonance imaging detects abnormalities in the lungs in children with bronchopulmonary dysplasia (BPD) as compared with age-matched normal children. MATERIALS AND METHODS: All experiments were compliant with Health Insurance Portability and Accountability Act (HIPAA) and performed with Food and Drug Administration approval under an IND application. The protocol was approved by our Institutional Review Board, and written informed consent was obtained. Hyperpolarized He diffusion-weighted magnetic resonance imaging was performed in 16 subjects with a history of preterm birth complicated by BPD (age range, 6.8 to 13.5 y; mean, 9.0 y) and in 29 healthy term-birth subjects (age range, 4.5-14.7 y; mean, 9.2 y) using a gradient-echo sequence with bipolar diffusion gradients and with measurements at 2 b values (0 and 1.6 s/cm). Age-related comparison of the whole-lung mean apparent diffusion coefficient (ADC), 90th percentile ADC, and percentage of whole-lung volume with ADC>0.2 cm/s between the 2 groups was examined using ordinary least-squares multiple regression. RESULTS: The mean ADC was significantly greater in subjects with BPD (0.187 vs. 0.152 cm/s, P<0.001). The 90th percentile ADC and mean percentage lung volume with ADC>0.2 cm/s were also higher in the BPD group (0.258 vs. 0.215 cm/s, 30.3% vs. 11.9%, P<0.001 for both). The body surface area-adjusted ventilated lung volume was similar in the 2 groups (1.93 vs. 1.91 L, P=0.90). CONCLUSIONS: Children with BPD had higher ADCs and the same lung volumes when compared with age-matched healthy subjects, suggesting that children with BPD have enlarged alveoli that are reduced in number.

Use of hyperpolarized helium-3 MRI to assess response to ivacaftor treatment in patients with cystic fibrosis.

BACKGROUND: This pilot study evaluated the effect of short- and long-term ivacaftor treatment on hyperpolarized 3He-magnetic resonance imaging (MRI)-defined ventilation defects in patients with cystic fibrosis aged ≥12years with a G551D-CFTR mutation. METHODS: Part A (single-blind) comprised 4weeks of ivacaftor treatment; Part B (open-label) comprised 48weeks of treatment. The primary outcome was change from baseline in total ventilation defect (TVD; total defect volume:total lung volume ratio). RESULTS: Mean change in TVD ranged from -8.2% (p=0.0547) to -12.8% (p=0.0078) in Part A (n=8) and -6.3% (p=0.1953) to -9.0% (p=0.0547) in Part B (n=8) as assessed by human reader and computer algorithm, respectively. CONCLUSIONS: TVD responded to ivacaftor therapy. 3He-MRI provides an individual quantification of disease burden that may be able to detect aspects of the disease missed by population-based spirometry metrics. Assessments by human reader and computer algorithm exhibit similar trends, but the latter appears more sensitive. www.clinicaltrials.gov identifier: NCT01161537.

Hyperpolarized Gas Magnetic Resonance Lung Imaging in Children and Young Adults.

The assessment of early pulmonary disease and its severity can be difficult in young children, as procedures such as spirometry cannot be performed on them. Computed tomography provides detailed structural images of the pulmonary parenchyma, but its major drawback is that the patient is exposed to ionizing radiation. In this context, magnetic resonance imaging (MRI) is a promising technique for the evaluation of pediatric lung disease, especially when serial imaging is needed. Traditionally, MRI played a small role in evaluating the pulmonary parenchyma. Because of its low proton density, the lungs display low signal intensity on conventional proton-based MRI. Hyperpolarized (HP) gases are inhaled contrast agents with an excellent safety profile and provide high signal within the lung, allowing for high temporal and spatial resolution imaging of the lung airspaces. Besides morphologic information, HP MR images also offer valuable information about pulmonary physiology. HP gas MRI has already made new contributions to the understanding of pediatric lung diseases and may become a clinically useful tool. In this article, we discuss the HP gas MRI technique, special considerations that need to be made when imaging children, and the role of MRI in 2 of the most common chronic pediatric lung diseases, asthma and cystic fibrosis. We also will discuss how HP gas MRI may be used to evaluate normal lung growth and development and the alterations occurring in chronic lung disease of prematurity and in patients with a congenital diaphragmatic hernia.

IgG4-Associated Cholangitis Can Mimic Hilar Cholangiocarcinoma.

IgG4-associated cholangitis can mimic hilar cholangiocarcinoma. Previously reported patients with IgG4-associated cholangitis mimicking cholangiocarcinoma had elevated serum IgG4 levels and long-segment biliary strictures. However, in the absence of other diagnostic criteria for malignancy, IgG4-associated cholangitis should remain a consideration among patients with normal serum IgG4 and a hilar mass suspicious for cholangiocarcinoma. The presence of a hilar mass and a malignant-appearing biliary stricture in two patients with normal serum IgG4 prompted further evaluation and subsequent concomitant liver and bile duct resection and reconstruction. The diagnosis of IgG4-associated cholangitis was established during the pathologic evaluation of the resected specimens. IgG4-associated cholangitis is a known imitator of hilar cholangiocarcinoma and should be considered in the differential diagnosis even among serologically IgG4-negative patients with a hilar mass prior to operative resection.

Effects of n-3 fish oil on metabolic and histological parameters in NASH: a double-blind, randomized, placebo-controlled trial.

BACKGROUND & AIMS: This study's aim was to assess the histological and metabolic effects of n-3 polyunsaturated fatty acids (PUFAs) vs. placebo while adjusting for the impact of age and weight change in NASH patients. (ClinicalTrials.gov: NCT00681408). METHODS: Forty-one subjects with non-cirrhotic NASH were enrolled, and 34 completed the study. 17 received n-3 fish oil 3000 mg/day and 17 received placebo daily for 1 year with typical counselling on caloric intake and physical activity for all subjects. RESULTS: N-3- and placebo-treated groups showed no significant difference for the primary end point of NASH activity score (NAS) reduction ⩾ 2 points without fibrosis progression after adjustment for known covariates (n-3, 4/17 (23.5%); placebo, 3/17, (17.6%), p = 0.99). Among subjects with increased or stable weight, n-3 subjects showed a larger decrease in liver fat content by MRI than placebo-treated subjects (p = 0.014 for 2nd quartile, p = 0.003 for 3rd quartile of weight change). N-3 treatment showed significant fat reduction on the paired analysis of image-assisted fat morphometry regardless of weight loss or gain. Exercise capacity remained markedly reduced in all subjects. No independent effects on markers of hepatocyte injury or insulin sensitivity indices were observed. CONCLUSION: N-3 PUFAs at 3000 mg/day for one year did not lead to an improvement in the primary outcome of histological activity in NASH patients (⩾ 2 point NAS reduction). N-3 led to reduced liver fat by multiple measures. Other metabolic effects were not seen, although no detrimental effects were apparent. Whether longer duration, higher dose, or different composition of n-3 therapy would lead to additional benefits is uncertain.

Rapid acquisition of helium-3 and proton three-dimensional image sets of the human lung in a single breath-hold using compressed sensing.

PURPOSE: To develop and validate a method for acquiring helium-3 ((3) He) and proton ((1) H) three-dimensional (3D) image sets of the human lung with isotropic spatial resolution within a 10-s breath-hold by using compressed sensing (CS) acceleration, and to assess the fidelity of undersampled images compared with fully sampled images. METHODS: The undersampling scheme for CS acceleration was optimized and tested using (3) He ventilation data. Rapid 3D acquisition of both (3) He and (1) H data during one breath-hold was then implemented, based on a balanced steady-state free-precession pulse sequence, by random undersampling of k-space with reconstruction by means of minimizing the L1 norm and total variance. CS-reconstruction fidelity was evaluated quantitatively by comparing fully sampled and retrospectively undersampled image sets. RESULTS: Helium-3 and (1) H 3D image sets of the lung with isotropic 3.9-mm resolution were acquired during a single breath-hold in 12 s and 8 s using acceleration factors of 2 and 3, respectively. Comparison of fully sampled and retrospectively undersampled (3) He and (1) H images yielded mean absolute errors <10% and structural similarity indices >0.9. CONCLUSION: By randomly undersampling k-space and using CS reconstruction, high-quality (3) He and (1) H 3D image sets with isotropic 3.9-mm resolution can be acquired within an 8-s breath-hold.

Phenotype of asthmatics with increased airway S-nitrosoglutathione reductase activity.

S-Nitrosoglutathione is an endogenous airway smooth muscle relaxant. Increased airway S-nitrosoglutathione breakdown occurs in some asthma patients. We asked whether patients with increased airway catabolism of this molecule had clinical features that distinguished them from other asthma patients. We measured S-nitrosoglutathione reductase expression and activity in bronchoscopy samples taken from 66 subjects in the Severe Asthma Research Program. We also analysed phenotype and genotype data taken from the program as a whole. Airway S-nitrosoglutathione reductase activity was increased in asthma patients (p=0.032). However, only a subpopulation was affected and this subpopulation was not defined by a "severe asthma" diagnosis. Subjects with increased activity were younger, had higher IgE and an earlier onset of symptoms. Consistent with a link between S-nitrosoglutathione biochemistry and atopy: 1) interleukin 13 increased S-nitrosoglutathione reductase expression and 2) subjects with an S-nitrosoglutathione reductase single nucleotide polymorphism previously associated with asthma had higher IgE than those without this single nucleotide polymorphism. Expression was higher in airway epithelium than in smooth muscle and was increased in regions of the asthmatic lung with decreased airflow. An early-onset, allergic phenotype characterises the asthma population with increased S-nitrosoglutathione reductase activity.

Lung injury induced by secondhand smoke exposure detected with hyperpolarized helium-3 diffusion MR.

PURPOSE: To determine whether helium-3 diffusion MR can detect the changes in the lungs of healthy nonsmoking individuals who were regularly exposed to secondhand smoke. MATERIALS AND METHODS: Three groups were studied (age: 59 ± 9 years): 23 smokers, 37 exposure-to-secondhand-smoke subjects, and 29 control subjects. We measured helium-3 diffusion values at diffusion times from 0.23 to 1.97 s. RESULTS: One-way analysis of variance revealed that the mean area under the helium-3 diffusion curves (ADC AUC) of the smokers was significantly elevated compared with the controls and to the exposure-to-secondhand-smoke subjects (P < 0.001 both). No difference between the mean ADC AUC of the exposure-to-secondhand-smoke subjects and that of the controls was found (P = 0.115). However, application of a receiver operator characteristic-derived rule to classify subjects as either a "control" or a "smoker," based on ADC AUC, revealed that 30% (11/37) of the exposure-to-secondhand subjects were classified as "smokers" indicating an elevation of the ADC AUC. CONCLUSION: Using helium-3 diffusion MR, elevated ADC values were detected in 30% of nonsmoking healthy subjects who had been regularly exposed to secondhand smoke, supporting the concept that, in susceptible individuals, secondhand smoke causes mild lung damage.

Ventilation-based segmentation of the lungs using hyperpolarized (3)He MRI.

PURPOSE: To develop an automated segmentation method to differentiate the ventilated lung volume on (3) He magnetic resonance imaging (MRI). MATERIALS AND METHODS: Computational processing (CP) for each subject consisted of the following three essential steps: 1) inhomogeneity bias correction, 2) whole lung segmentation, and 3) subdivision of the lung segmentation into regions of similar ventilation. Evaluation consisted of two comparative analyses: i) comparison of the number of defects scored by two human readers in 43 subjects, and ii) simultaneous truth and performance level estimation (STAPLE) in 18 subjects in which the ventilation defects were manually segmented by four human readers. RESULTS: There was excellent correlation between the number of ventilation defects tabulated by CP and reader #1 (intraclass correlation coefficient [ICC] = 0.86), CP and reader #2 (ICC = 0.85), and between the two readers (ICC = 0.97). The STAPLE results from the second analysis yielded the following sensitivity/specificity numbers: CP (0.898/0.905), radiologist #1 (0.743/0.897), radiologist #2 (0.501/0.985), radiologist #3 (0.898/0.848), and the first author (0.600/0.984). CONCLUSION: We developed and evaluated an automated method for quantifying the ventilated lung volume on (3) He MRI. The findings strongly indicate that our proposed algorithmic processing may be a reliable, automatic method for quantitating ventilation defects.

Pancreas-protocol imaging at a high-volume center leads to improved preoperative staging of pancreatic ductal adenocarcinoma.

BACKGROUND: High-quality preoperative cross-sectional imaging is vital to accurately stage patients with pancreatic ductal adenocarcinoma (PDAC). We hypothesized that imaging performed at a high-volume pancreatic cancer center with pancreatic imaging protocols more accurately stages patients compared with pre-referral imaging. METHODS: We retrospectively reviewed data from all patients with PDAC who presented to the surgical oncology clinic at our institution between June 2005 and August 2009. Detailed preoperative imaging, staging, and operative data were collected for each patient. RESULTS: A total of 230 patients with PDAC were identified, of which 169 had pre-referral imaging. Patients were selectively reimaged at our institution based on the quality and timing of imaging at the outside facility: 108 (47%) patients were deemed resectable, 54 (23.5%) were deemed borderline-resectable, and 68 (29.5%) were deemed unresectable. Of the resectable patients, 99 opted for resection. Eighty-two of those 99 patients underwent preoperative imaging at our institution, and of these 27% had unresectable disease at the time of surgery compared with 47% of patients who only had pre-referral imaging (p = 0.14). Reimaging altered staging and changed management in 56% of patients. Among that group were 55 patients, categorized as resectable on pre-referral imaging, who on repeat imaging were deemed to be borderline resectable (n = 27) or unresectable (n = 28). CONCLUSIONS: Pancreas-protocol imaging at a high-volume center improves preoperative staging and alters management in a significant proportion of patients with PDAC who undergo pre-referral imaging. Thus, repeat imaging with pancreas protocols and dedicated radiologists is justified at high-volume centers.

Comparison between endoscopic ultrasound and magnetic resonance imaging for the staging of pancreatic cancer.

OBJECTIVE: Preoperative staging of pancreatic cancer is crucial for proper therapy. Through this study, we aimed to compare the ability of endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) to effectively detect and stage pancreatic cancer. METHODS: One hundred twenty-seven patients undergoing EUS-fine-needle aspiration and MRI for the workup of pancreatic cancer were captured in a prospective database for comparison. The final surgical stage was recorded in patients who went to surgery. RESULTS: Of 127 patients, 48 were surgically explored, and of these, 22 (46%) underwent pancreaticoduodenectomy. Agreement in the patients' staging between EUS and MRI was 94 (74%) of 127. Magnetic resonance imaging was more likely to report metastatic disease or arterial involvement. The overall correlation between EUS and MRI was marginal (κ = 0.42; 95% CI, 0.26-0.58). Of the 48 surgically explored patients, 12 (25%) were understaged by MRI, 13 (27%) were understaged by EUS, and 1 (2%) were overstaged. Endoscopic US and MRI had a sensitivity of 34 (97.2%) of 35 for stage II tumors and 35 (100%) of 35 for lower-stage tumors, respectively. CONCLUSION: Endoscopic US and MRI had marginal correlation for staging, especially the more advanced tumors. Although EUS has the added advantage of tissue acquisition for confirmation, the tumors understaged by both the modalities were different. Therefore, both tests should be performed for accurate staging.

Preoperative capecitabine and concurrent radiation for borderline resectable pancreatic cancer.

BACKGROUND: Patients with borderline resectable pancreatic ductal adenocarcinoma (PDA) represent a high-risk group of patients due to tumor or patient-related characteristics. The optimal management of these patients has not been fully defined. MATERIALS AND METHODS: All patients undergoing evaluation for PDA between 2005 and 2008 were identified. Clinical, radiographic, and pathological data were retrospectively reviewed. Patients were staged as borderline resectable using the M.D. Anderson Cancer Center (MDACC) classification. RESULTS: A total of 170 patients with PDA were identified, 40 with borderline resectable disease. Of these, 34 borderline resectable patients (85%) completed neoadjuvant therapy and were restaged; pancreatic resection was completed in 16 patients (46%). Also, 8 patients completed 50 Gy of radiation in 28 fractions in 6 weeks, whereas 8 patients received 50 Gy in 20 fractions in 4 weeks plus chronomodulated capecitabine. An R0 resection was achieved in 12 of the 16 patients (75%). Also, 5 patients (63%) treated in 20 fractions had >90% pathologic response versus 1 (13%) treated in 28 fractions (P < .05). Borderline resectable patients completing surgery had similar survival to patients with resectable disease who underwent surgery. Patients receiving accelerated fractionation radiation had improved survival compared with patients treated with standard fractionation protocol. CONCLUSIONS: A neoadjuvant approach to borderline resectable PDA identifies patients who are most likely to benefit from pancreatic resection. Preoperative capecitabine-based chemoradiation is an effective, well-tolerated treatment for these patients. Neoadjuvant therapy for borderline resectable PDA warrants further investigation using treatment schedules that can safely intensify irradiation dose.

Dynamic MRI of grid-tagged hyperpolarized helium-3 for the assessment of lung motion during breathing.

PURPOSE: To develop a dynamic magnetic resonance imaging (MRI) tagging technique using hyperpolarized helium-3 (HP He-3) to track lung motion. METHODS AND MATERIALS: An accelerated non-Cartesian k-space trajectory was used to gain acquisition speed, at the cost of introducing image artifacts, providing a viable strategy for obtaining whole-lung coverage with adequate temporal resolution. Multiple-slice two-dimensional dynamic images of the lung were obtained in three healthy subjects after inhaling He-3 gas polarized to 35%-40%. Displacement, strain, and ventilation maps were computed from the observed motion of the grid peaks. RESULTS: Both temporal and spatial variations of pulmonary mechanics were observed in normal subjects, including shear motion between different lobes of the same lung. CONCLUSION: These initial results suggest that dynamic imaging of grid-tagged hyperpolarized magnetization may potentially be a powerful tool for observing and quantifying pulmonary biomechanics on a regional basis and for assessing, validating, and improving lung deformable image registration algorithms.

Helium-3 diffusion MR imaging of the human lung over multiple time scales.

RATIONALE AND OBJECTIVES: Diffusion magnetic resonance imaging (MRI) with hyperpolarized (3)He gas is a powerful technique for probing the characteristics of the lung microstructure. A key parameter for this technique is the diffusion time, which is the period during which the atoms are allowed to diffuse within the lung for measurement of the signal attenuation. The relationship between diffusion time and the length scales that can be explored is discussed, and representative, preliminary results are presented from ongoing studies of the human lung for diffusion times ranging from milliseconds to several seconds. MATERIALS AND METHODS: (3)He diffusion MRI of the human lung was performed on a 1.5T Siemens Sonata scanner. Using gradient echo-based and stimulated echo-based techniques for short and medium-to-long diffusion times, respectively, measurements were performed for times ranging from 2 milliseconds to 6.5 seconds in two healthy subjects, a subject with subclinical chronic obstructive pulmonary disease and a subject with bronchopulmonary dysplasia. RESULTS: In healthy subjects, the apparent diffusion coefficient decreased by about 10-fold, from approximately 0.2 to 0.02 cm(2)/second, as the diffusion time increased from approximately 1 millisecond to 1 second. Results in subjects with disease suggest that measurements made at diffusion times substantially longer than 1 millisecond may provide improved sensitivity for detecting certain pathologic changes in the lung microstructure. CONCLUSIONS: With appropriately designed pulse sequences it is possible to explore the diffusion of hyperpolarized (3)He in the human lung over more than a 1,000-fold variation of the diffusion time. Such measurements provide a new opportunity for exploring and characterizing the microstructure of the healthy and diseased lung.

Multimodality Treatment With Helical Tomotherapy Intensity Modulated Radiotherapy, Capecitabine, and Photodynamic Therapy is Feasible and Well Tolerated in Patients With Hilar Cholangiocarcinoma.

BACKGROUND AND PURPOSE: Unresectable cholangiocarcinoma is an intractable disease marked by recurrent bouts of biliary obstruction and infection. Traditional treatment methods provide only symptomatic relief and no proven survival advantage. We assessed the tolerability of helical tomotherapy intensity modulated radiotherapy (IMRT) with concurrent capecitabine and photodynamic therapy (PDT) in patients with unresectable hilar cholangiocarcinoma. METHODS: Ten patients with unresectable hilar cholangiocarcinoma were treated with helical tomotherapy IMRT. An accelerated dose of 50 Gy in 20 fractions (2.5 Gy/fraction) was used. Planning target volume (PTV) consisted of a 1.5 cm radial expansion and a 2 cm craniocaudal expansion of the magnetic resonance imaging and/or contrast enhanced computed tomography-defined gross target volume. PTV ranged from 123 cc to 693 cc (mean 349 cc). Concurrent chronomodulated capecitabine was administered on days of irradiation. Six patients received PDT. RESULTS: All patients developed side effects, including grade 2 nausea, and 9 of 10 experienced mild fatigue. Patients lost 3% of their body weight on average. Three patients required brief hospital admission and stent revision for cholangitis during chemoradiotherapy. Capecitabine was discontinued in one patient and decreased in dose for another due to increasing liver enzymes. Median overall survival was 13 months, and median disease-free survival was 10 to 11 months. One patient underwent successful cadaveric liver transplant after chemoradiotherapy and remains disease free 2 years later. CONCLUSIONS: Concurrent chemoradiotherapy with helical tomotherapy IMRT and capecitabine in conjunction with PDT is well tolerated in patients with hilar cholangiocarcinoma.