New insights into lung diseases using hyperpolarized gas MRI.

Hyperpolarized (HP) gases are a new class of contrast agents that permit to obtain high temporal and spatial resolution magnetic resonance images (MRI) of the lung airspaces. HP gas MRI has become important research tool not only for morphological and functional evaluation of normal pulmonary physiology but also for regional quantification of pathologic changes occurring in several lung diseases. The purpose of this work is to provide an introduction to MRI using HP noble gases, describing both the basic principles of the technique and the new information about lung disease provided by clinical studies with this method. The applications of the technique in normal subjects, smoking related lung disease, asthma, and cystic fibrosis are reviewed.

MR grid-tagging using hyperpolarized helium-3 for regional quantitative assessment of pulmonary biomechanics and ventilation.

A new technique is demonstrated in six healthy human subjects that combines grid-tagging and hyperpolarized helium-3 MRI to assess regional lung biomechanical function and quantitative ventilation. 2D grid-tagging, achieved by applying sinc-modulated RF-pulse trains along the frequency- and phase-encoding directions, was followed by a multislice fast low-angle shot (FLASH)-based acquisition at inspiration and expiration. The displacement vectors, first and second principal strains, and quantitative ventilation were computed, and mean values were calculated for the upper, middle, and lower lung regions. Displacements in the lower region were significantly greater than those in either the middle or upper region (P < 0.005), while there were no significant differences between the three regions for the two principal strains and quantitative ventilation (P = 0.11-0.92). Variations in principal strains and ventilation were greater between subjects than between lung zones within individual subjects. This technique has the potential to provide insight into regional biomechanical alterations of lung function in a variety of lung diseases.

Hyperpolarized 3He lung ventilation imaging with B1-inhomogeneity correction in a single breath-hold scan.

The signal-to-noise ratio (SNR) of hyperpolarized noble gas MR images is sensitive to the flip angle used. Variations in flip angle due to B1-inhomogeneity of the RF coil cause intensity variation artifacts in lung ventilation images which may mask or mimic disease. We show these artifacts can be minimized by using the optimal flip angle and corrected if the local flip angle is known. Hyperpolarized 3He lung images were obtained in ten healthy subjects using both a conventional gradient-echo sequence and a new hybrid pulse sequence designed to simultaneously acquire lung ventilation images and corresponding flip-angle maps in comparable imaging time. Flip-angle maps and corrected images were calculated from the hybrid scan and compared with conventional images. The qualitative theoretical dependence of flip angle on SNR was verified. Ventilation images and flip-angle maps were successfully obtained with the hybrid sequence. Corrections to image intensity calculated from the flip-angle maps appeared reasonable for images acquired using an average flip angle near optimal. Use of the optimal flip angle is crucial to the quality of lung ventilation images. Artifactual intensity variations due to RF-coil inhomogeneity may be identified and potentially corrected using our hybrid sequence.

Dynamic spiral MRI of pulmonary gas flow using hyperpolarized (3)He: preliminary studies in healthy and diseased lungs.

An optimized interleaved-spiral pulse sequence, providing high spatial and temporal resolution, was developed for dynamic imaging of pulmonary ventilation with hyperpolarized (3)He, and tested in healthy volunteers and patients with lung disease. Off-resonance artifacts were minimized by using a short data-sampling period per interleaf, and gradient-fidelity errors were compensated for by using measured k-space trajectories for image reconstruction. A nonsequential acquisition order was implemented to improve image quality during periods of rapid signal change, such as early inspiration. Using a sliding-window reconstruction, cine-movies with a frame rate of 100 images per second were generated. Dynamic images demonstrating minimal susceptibility- and motion-induced artifacts were obtained in sagittal, coronal, and axial orientations. The pulse sequence had the flexibility to image multiple slices almost simultaneously. Our initial experience in healthy volunteers and subjects with lung pathology demonstrated the potential of this new tool for capturing the features of lung gas-flow dynamics.

Hyperpolarized noble gas MR imaging of the lung: potential clinical applications.

Hyperpolarized noble gases are a new class of MR contrast agent. Since the first hyperpolarized gas MR images of the lung were reported, there has been considerable interest in using hyperpolarized gas to obtain high spatial and temporal resolution images of the air spaces of the lung. In addition to static images of lung ventilation, new techniques are being developed using hyperpolarized gas to obtain dynamic, diffusion and oxygen concentration images of the lung. In this article, we review the potential clinical applications of pulmonary hyperpolarized gas MRI and discuss the preliminary findings in a variety of lung diseases. Hyperpolarized gas MRI has the potential to provide a comprehensive morphologic and functional assessment of the lung.

Minimally invasive surgery for solitary parathyroid adenomas in patients with primary hyperparathyroidism: role of US with supplemental CT.

PURPOSE: To determine the role of ultrasonography (US) with supplemental computed tomography (CT) in patients with primary hyperparathyroidism who undergo minimally invasive surgery instead of conventional neck exploration. MATERIALS AND METHODS: US and CT were performed in 61 consecutive patients with primary hyperparathyroidism (part 1) to identify and localize solitary adenomas for resection by means of minimally invasive surgery and to provide a surgical road map. In part 2, involving 33 consecutive patients, CT was performed only when no solitary adenoma was identified with US or for road map information. Minimally invasive surgery was considered successful when serum calcium levels normalized and remained stable. RESULTS: In part 1, 46 definite solitary adenomas were found with US and two additional ones with CT. Minimally invasive surgery was successful in 45 patients and failed once. In part 2, US helped identify 23 solitary adenomas, and CT helped to find one. Minimally invasive surgery was successful in 22 patients and failed in two. Combined results in 94 patients demonstrated successful minimally invasive surgery in 67 (71%), with 64 of them selected with US alone (95% CI: 61, 80). The sensitivity of US in the diagnosis of solitary adenoma was 78% (95% CI: 67%, 86%), with a positive predictive value of 96% (95% CI: 88%, 99%). CONCLUSION: US examination of patients with primary hyperparathyroidism allowed successful selection for minimally invasive surgery in more than two-thirds of the cases, with additional CT useful chiefly for surgical road mapping.

Assessing the subtalar joint: the Brodén view revisited.

We prospectively evaluated subtalar inversion stress views (Brodén view) with inversion stress views on helical CT in a group of 10 patients with unilateral instability. The contralateral, asymptomatic ankle was used as control. All patients were examined with inversion stress views on plain stress radiography and helical CT. Subtalar tilt was demonstrated in all cases on conventional stress radiography. Helical CT didn't show tilting in any of the patients except in the subluxated posteromedial part of the subtalar joint. Our data do not support prior reports that the Brodén view is useful for screening patients with subtalar instability.

Hyperpolarized 3He MR lung ventilation imaging in asthmatics: preliminary findings.

Asthma is a disease characterized by chronic inflammation and reversible obstruction of the small airways resulting in impaired pulmonary ventilation. Hyperpolarized 3He magnetic resonance (MR) lung imaging is a new technology that provides a detailed image of lung ventilation. Hyperpolarized 3He lung imaging was performed in 10 asthmatics and 10 healthy subjects. Seven asthmatics had ventilation defects distributed throughout the lungs compared with none of the normal subjects. These ventilation defects were more numerous and larger in the two symptomatic asthmatics who had abnormal spirometry. Ventilation defects studied over time demonstrated no change in appearance over 30-60 minutes. One asthmatic subject was studied twice in a three-week period and had ventilation defects which resolved and appeared in that time. This same subject was studied before and after bronchodilator therapy, and all ventilation defects resolved after therapy. Hyperpolarized 3He lung imaging can detect the small, reversible ventilation defects that characterize asthma. The ability to visualize lung ventilation offers a direct method of assessing asthmatics and their response to therapy.

Imaging and clinical characteristics of focal atrophy of segments 2 and 3 in primary sclerosing cholangitis.

BACKGROUND AND AIMS: Focal atrophy in primary sclerosing cholangitis (PSC) is usually thought to result from severe biliary stricture and focal biliary cirrhosis. Atrophy of the left lateral segments (segments 2 and 3) are striking when observed grossly. This type of atrophy may be subtle on cross-sectional imaging and by endoscopic retrograde cholangiopancreatography (ERCP) because of the peripheral location and compensatory hypertrophy of other parts of the liver. We examined 44 consecutive PSC patients to determine the incidence and clinical characteristics of this abnormality, and to correlate imaging studies with the gross appearance. METHODS: We reviewed all cases of PSC encountered over a 3 year period ascertained from the liver disease registry. Magnetic resonance imaging or CT images were re-examined for evidence of segment 2 and 3 atrophy. RESULTS: Four of 44 patients had focal segment 2 and 3 atrophy. These four had been confirmed laparoscopically or by inspection of the liver explant. The remaining segments of the liver were relatively spared of injury in two of the patients, and three of the four patients had preserved synthetic function without evidence of portal hypertension. While the abnormality is clearly visible on cross-sectional imaging, its peripheral location caused it to be an unobtrusive. Likewise, ERCP did not clearly reveal the abnormality on initial inspection. CONCLUSIONS: We conclude that focal atrophy of segments 2 and 3 is a sometimes early and subtle finding in PSC that may be overlooked in cross-sectional imaging or ERCP unless specifically sought.

Antegrade ureteral stent placement: positioning without use of a retraction string.

PURPOSE: To evaluate a simple method of antegrade ureteral stent insertion allowing optimal positioning of the stent without the use of a retraction string. PATIENTS AND METHODS: Seventeen stents were placed in sixteen patients with ureteral obstruction. Materials included a long vascular introducer sheath and radiopaque markers on the tips of both the sheath and the pusher catheter. For optimal positioning of the proximal pigtail in the renal pelvis, the distal end of the sheath was used to hold a large portion of the pigtail in the extended state prior to its deployment. RESULTS: All stent placements were successful. In one case, the tip of the proximal pigtail was caught in a lower-pole calix. In another case, repeat stent placement was necessary because of recurrent stricture several months after removal of the first stent. All stents functioned properly, as demonstrated by follow-up nephrostography 2 or 3 days after each procedure. CONCLUSION: The insertion method we describe is simple, easy to perform, and fast and avoids the risks associated with the use of a retraction string.

Posttraumatic subchondral bone contusions and fractures of the talotibial joint: occurrence of "kissing" lesions.

OBJECTIVE: The objective of this study was to determine the presence and location of subchondral bone contusions, fractures, and "kissing" lesions of the talotibial joint after a sprain of the ankle shown on MR imaging. MATERIALS AND METHODS: We retrospectively reviewed the images of all consecutive patients who underwent MR imaging of the ankle after acute or recurrent sprain occurring between January and December 1997. The number and location of subchondral contusions or fractures revealed on MR imaging were recorded, and a comparison was made with the radiographs obtained for each patient. RESULTS: Of the 146 ankles, 42 osteochondral lesions were revealed on MR imaging in 26 ankles (18%) involving 23 patients. Twenty-three lesions were localized in the dome of the talus and 19, in the tibiofibular plafond. In 16 (11%) of the 146 ankles, the lesions were present in the opposing bones of the joint ("kissing" lesions). Only six of the 12 talar fractures and none of the tibial fractures involving the 26 ankles were seen on conventional radiography. CONCLUSION: Subchondral lesions in the talus and tibia are relatively common after ankle trauma, occurring in 18% of patients in our series. Kissing lesions were present in more than half of the lesions in these patients.

Duplex ultrasonography in assessing restenosis of renal artery stents.

PURPOSE: To determine the accuracy and optimal threshold values of duplex ultrasonography (US) in assessing restenosis of renal artery stents. METHODS: Twenty-four consecutive patients with 33 renal arteries that had previously been treated with placement of a Palmaz stent underwent duplex US prior to intraarterial digital subtraction angiography (DSA), which was the reference standard. Diagnostic accuracy of in-stent peak systolic velocity (PSV) and reno-aortic ratio (RAR = PSV renal stent/PSV aorta) in detecting > 50% in-stent restenosis were evaluated by the receiver operating characteristic curve. Sensitivity and specificity were determined using the optimal threshold values, and using published threshold values: RAR > 3.5 and in-stent PSV > 180 cm/sec. RESULTS: Six examinations were technically inadequate. Nine stents had residual or restenosis > 50% at DSA. The two duplex parameters were equally accurate since areas under the curves were similar (0.943). With optimal threshold values of 226 cm/sec for PSV and 2.7 for RAR, sensitivities and specificities were 100% and 90%, and 100% and 84%, respectively. Using the published duplex criteria resulted in sensitivities and specificities of 100% and 74% for PSV, and 50% and 89% for RAR. CONCLUSION: Duplex US is a sensitive modality for detecting in-stent restenosis if laboratory-specific threshold values are used.

A multisite phase III study of the safety and efficacy of a new manganese chloride-based gastrointestinal contrast agent for MRI of the abdomen and pelvis.

The purpose of this study was to evaluate the safety and efficacy of a manganese chloride-based oral magnetic resonance (MR) contrast agent during a Phase III multisite clinical trial. Two hundred seventeen patients were enrolled who were already scheduled for MRI of the abdomen and/or pelvis. In this group of patients, it was postulated that the use of an oral agent would better allow discrimination of pathology from bowel. Patients with known gastrointestinal pathology including peptic ulcer disease, inflammatory bowel disease, obstruction, or perforation were excluded to minimize confounding variables that could affect the safety assessment. Of these 217 patients, 18 received up to 900 mL of placebo, and 199 patients were given up to 900 mL of a manganese chloride-based oral contrast agent, LumenHance (Bracco Diagnostics, Inc.). Safety was determined by comparing pre- and post-dose physical examinations, vital signs, and laboratory examinations and by documenting adverse events. Efficacy was assessed by unblinded site investigators and two blinded reviewers who compared pre- and post-dose T1- and T2-weighted MRI scans of the abdomen and/or pelvis. In 111 (57%) of the 195 cases evaluated for efficacy by site investigators (unblinded readers), MRI after LumenHance provided additional diagnostic information. Increased information was found by two blinded readers in 52% and 51% of patients, respectively. In 44/195 cases (23%) unblinded readers felt the additional information would have changed patient diagnosis and in 50 patients (26%), it would have changed management and/or therapy. Potential changes in patient diagnosis or management/therapy were seen by the two blinded readers in 8-20% of patients. No clinically significant post-dose laboratory changes were seen. Forty-eight patients (24%) receiving LumenHance and four patients (22%) receiving placebo experienced one or more adverse events. Gastrointestinal tract side effects were most common, seen in 29 (15%) of LumenHance patients and in 3 (17%) of the placebo patients. LumenHance is a safe and efficacious oral gastrointestinal contrast agent for MRI of the abdomen and pelvis.

Renal volume measurements: accuracy and repeatability of US compared with that of MR imaging.

PURPOSE: To determine the accuracy and repeatability of ultrasonography (US) with the ellipsoid formula in calculating the renal volume. MATERIALS AND METHODS: The renal volumes in 20 volunteers aged 19-51 years were determined by using US with the ellipsoid formula and magnetic resonance (MR) imaging with the voxel-count method by two independent observers for each modality. The observers performed all measurements twice, with an interval between the first and second examinations. The voxel-count method was the reference standard. Repeatability was evaluated by calculating the SD of the difference (method of Bland and Altman). RESULTS: Renal volume was underestimated with US by 45 mL (25%) on average. A comparable underestimation was found when the ellipsoid formula was applied to MR images. This indicates that the inaccuracy of US renal volume measurements (a) occurred because the kidney does not resemble an ellipsoid and (b) was not primarily related to the imaging modality. Intra- and interobserver variations in US volume measurements were poor; the SD of the difference was 21-32 mL. For comparison, the SD of the difference in reference-standard measurements was 5-10 mL. CONCLUSION: Use of US with the ellipsoid formula is not appropriate for accurate and reproducible calculation of renal volume.

An in vivo evaluation of the reproducibility of intima-media thickness measurements of the carotid artery segments using B-mode ultrasound.

B-mode ultrasound may be used to measure the intima-media thickness (IMT) in subjects with a history of atherosclerosis. The variability between measurements depends on the subjective interpretation of ultrasonographers and readers. The two carotid arteries, subdivided in common (CCA), bulbus (BUL) and internal (ICA) of 10 men with proven coronary disease, were scanned twice by two ultrasonographers with a 1-week interval. The IMTs were measured off-line by two readers. The number of IMT measurements was 75 (94%) of 80 in the CCA, 61 (76%) of 80 in the BUL and 43 (54%) of 80 in the ICA segment. In the CCA segment, the agreement between readers (mean = 0.02 mm; limits: -0.26 to +0.3 mm) and between visits for each reader separately (reader 1: mean = 0.01 mm; limits: -0.33 to +0.35 mm and, reader 2: mean = 0.04 mm; limits: -0.36 to +0.44 mm) was better than in the more distal segments. Therefore, it is concluded that IMT measurements are best performed in the CCA segment.

Lung air spaces: MR imaging evaluation with hyperpolarized 3He gas.

Thirty-two magnetic resonance imaging examinations of the lungs were performed in 16 subjects after inhalation of 1-2 L of helium 3 gas that was laser polarized to 10%-25%. The distribution of the gas was generally uniform, with visualization of the fissures in most cases. Ventilation defects were demonstrated in smokers and in a subject with allergies. The technique has potential for evaluating small airways disease.

Safety profile of ultrasmall superparamagnetic iron oxide ferumoxtran-10: phase II clinical trial data.

The safety data from the phase II clinical trial of ferumoxtran-10, an ultrasmall superparamagnetic iron oxide contrast agent, are presented. One hundred and four patients with focal liver or spleen pathologies underwent ferumoxtran-10-enhanced magnetic resonance (MR) imaging at doses of 0.8, 1.1, and 1.7 mg Fe/kg. Overall, 15% patients reported a total of 33 adverse events, regardless of causality. The adverse events most frequently seen were dyspnea (3.8%), chest pain (2.9%), and rash (2.9%). No serious adverse events were reported during the 48 hour observation period. There were no clinically significant effects on vital signs, physical examination, and laboratory results. Ferumoxtran-10 is a safe and well tolerated MR contrast agent.

Effect of age on cerebral blood flow: measurement with ungated two-dimensional phase-contrast MR angiography in 250 adults.

PURPOSE: To determine the normal values and effects of age and sex on total cerebral blood flow (CBF) as measured with ungated two-dimensional phase-contrast magnetic resonance (MR) angiography. MATERIALS AND METHODS: Volume flow rates in the basilar artery and both internal carotid arteries were measured on two-dimensional phase-contrast MR angiograms obtained in 250 subjects (age range, 19-88 years; mean age, 50 years) undergoing MR imaging because of indications other than cerebrovascular disease. Volume flow rates for the three arteries were summed to obtain the total CBF, and the values were analyzed in terms of age and sex. RESULTS: Mean total CBF was 616 mL/min +/- 143. There was a significant yearly decrease with age in total CBF of 4.8 mL/min (P < .001). Mean total CBF ranged from 748 mL/min +/- 121 to 474 mL/min +/- 105 in subjects aged 19-29 and 80-89 years, respectively. No sex differences were found. Mean relative contributions of the right and left internal carotid arteries and the basilar artery to total CBF were 41%, 40%, and 19%, respectively, with no substantial change due to age. CONCLUSION: Ungated two-dimensional phase-contrast MR angiography is a useful, noninvasive technique for assessing total CBF. By using this technique, a significant decrease in total CBF with age was demonstrated.

In vitro measurement of kidney size: comparison of ultrasonography and MRI.

In this in vitro study, the accuracy and repeatability of magnetic resonance imaging (MRI) and ultrasound (US) in assessing renal length and volume were determined. US and MR images of 20 cadaver pig kidneys were obtained twice and evaluated by two observers for each modality. The fluid displacement method provided the "gold standard." Renal volumes were calculated from the US and MR images using the ellipsoid formula. Additional volume calculations after segmentation of the kidney on MR images were done using the voxel-count method. Volumes calculated with the ellipsoid formula resulted in an average of 24% underestimation (range 5%-48%) of the renal volume for both US and MRI. With the voxel-count method, no significant deviation from the true renal volume was encountered. Repeatability was also greatest with the voxel-count method. Measuring renal length, repeatability was, again, better with MRI compared to US. For reliable calculation of renal size in vitro, MRI with use of the voxel-count method is preferred.