Magnetic resonance imaging of breast cancer angiogenesis: a review.

The development and growth of solid tumors rely on a process known as perfusion which allows for the delivery and clearance of nutrients through their vasculature. The classical approach of studying tumor vasculature by histologic staining of endothelial cells provides a measure of microvessel density in areas of high vascularization (so-called "hot spots"). More advanced high-resolution, parametric, contrast-enhanced MRI techniques enable quantitative assessment of the vascular distribution and function over the entire tumor. Hence, MRI overcomes the intratumoral variation of the histological method. Clinical testing of the MRI approach, that evaluates the permeability and surface area of the tumor vasculature, demonstrates improved accuracy of breast cancer diagnosis.

Critical role of spatial resolution in dynamic contrast-enhanced breast MRI.

The spatial resolution of three-dimensional (3D) gradient-echo T1-weighted images, from 40 women with 25 malignant and 23 benign lesions, was purposely degraded to determine the role of spatial resolution in recording, analysis, and diagnosis of dynamic contrast-enhanced breast MRI. Images were recorded and analyzed at pixel resolution according to the 3TP method (Degani et al., Nat Med 1997;3:780-782). Reduction in spatial resolution degraded the appearance of foci with fast wash-in and fast washout dynamics. This resulted in an increase in false-negative diagnoses. The sensitivity for differentiating between malignant and benign lesions, using threshold criteria defined by the 3TP analysis, of 76% decreased to 60% and 24% for a 2- and 4-fold reduction in spatial resolution, respectively, without affecting significantly the high specificity (96-100%). In order to minimize false-negative diagnoses of contrast-enhanced breast MRI and maintain high specificity, it is essential to record and analyze the dynamic behavior at high spatial resolution. J. Magn. Reson. Imaging 2001;13:862-867.

CT versus sonography for monitoring radiofrequency ablation in a porcine liver.

OBJECTIVE: The objective of this study was to compare CT and sonography for monitoring radiofrequency (RF) lesions in porcine livers. SUBJECTS AND METHODS: RF lesions (n = 12) were created in three pig livers by applying 13 min of current to a multielectrode RF probe with a target temperature of 95 degrees C. Helical unenhanced CT and corresponding axial sonography were performed before ablation, at 2 min, 8 min, and immediately after ablation. Contrast-enhanced CT was performed after ablation. CT scans and sonograms were evaluated by blinded observers for conspicuity of the RF lesion, edge detection (visibility of liver-lesion interface), and artifacts. Hounsfield units were recorded at every time interval, and radiologic-pathologic correlation for lesion size and configuration was performed. RESULTS: Mean size of RF lesions was 3. 03 +/- 0.9 cm. On CT, RF lesions had consistently lower attenuation values than surrounding liver (22.2 H lower than liver at 8 min, p < 0.0001). Echogenicity was variable with sonography (hypoechoic = 59%, hyperechoic = 25%, isoechoic = 16%). Unenhanced CT significantly improved conspicuity, edge detection of RF lesions, and decreased artifacts compared with sonography (p < 0.05). Contrast-enhanced CT improved RF lesion detection, border discrimination, and artifacts compared with sonography (p < 0.05). Unenhanced CT had the best correlation to pathologic size (r = 0.74), followed by contrast-enhanced CT (r = 0.72) and sonography (r = 0.56). Contrast-enhanced CT best correlated with lesion shape, but slightly overestimated size because of areas of ischemia peripheral to the RF lesion. CONCLUSION: In this animal model, unenhanced CT was an effective way to monitor RF ablation compared with sonography because of increased lesion discrimination, reproducible decreased attenuation during ablation, and improved correlation to pathologic size.

Accurate and rapid quantitative dynamic contrast-enhanced breast MR imaging using spoiled gradient-recalled echoes and bookend T(1) measurements.

A method is presented that converts dynamic T(1)-weighted spoiled gradient-recalled echo (SGRE) image intensities into estimates of T(1) without the errors associated with imperfections in the slice profile and transmitter coil magnetic field (B(1)). The method involves T(1) measurements performed before and after a series of dynamic SGRE images. These measurements serve to calibrate and correct the SGRE signal strength equation used to estimate T(1). Simulations and phantom experiments were performed to test the method for slice-selective (two-dimensional) and slab-selective (three-dimensional) imaging, as well as for imaging performed with optimized and un-optimized B(1). For nearly all test conditions, T(1) was estimated accurately (within 10%) over a range of T(1) values expected in vivo ( approximately 1200 --> 300 msec). This method should be useful for quantifying dynamic SGRE imaging for many different applications including breast MR imaging. Magn Reson Med 42:746-753, 1999.

Limitations of the keyhole technique for quantitative dynamic contrast-enhanced breast MRI.

The effect of keyhole data acquisition on quantitative analysis of dynamic MRI was examined. Experiments were performed retrospectively on raw data obtained from clinical dynamic contrast-enhanced breast imaging procedures. The effects of keyhole phase-encoding acquisition and type of reconstruction algorithm on the accuracy of derived quantitative parameters was assessed. Results indicate that the minimum keyhole size used should be restricted by the approximate minimum size of the expected lesions. Furthermore, reconstruction algorithms that offer improved image resolution do not circumvent this restriction.

Application of a quantitative model to differentiate benign from malignant breast lesions detected by dynamic, gadolinium-enhanced MRI.

Both benign and malignant breast lesions may exhibit intense contrast enhancement when imaged using gadolinium-enhanced MRI. We propose a quantitative approach for fitting dynamic signal intensity (SI) data that may distinguish benign from malignant lesions. We studied 78 lesions in 75 women (18 malignancies, 16 fibroadenomas, and 44 other benign breast lesions) to determine the potential of this model for decreasing false-positive MR results. Twenty-eight lesions showed no enhancement; all were benign. One lesion showed a complex pattern not amenable to region-of-interest analysis and was considered a false positive. SI versus time data for the remaining 49 lesions were fit to the proposed model. We found that one parameter, M, the normalized slope of the SI enhancement profile evaluated at half the maximal signal intensity, seemed to be highly correlated with malignancy and offered improved discrimination between malignant and benign lesions compared to a previously published two-point slope method.

A randomized comparison of iodixanol and iohexol in adult body computed tomography scanning.

RATIONALE AND OBJECTIVES: We compared the safety and imaging efficacy of iodixanol-270 (270 mg I/ml), iodixanol-320 (320 mg I/ml), both of which are isosmolal to blood, and iohexol-300 (300 mg I/ml) for body computed tomography (CT) scanning. METHODS: One hundred twenty-six patients from the University of Wisconsin Hospital and Temple University Hospital scheduled to undergo body CT examinations were randomly assigned to receive either iodixanol-270, iodixanol-320, or iohexol-300. Patients were monitored with questioning and vital signs before injection, immediately after injection, and at 24 and 48 hr. Extensive laboratory evaluation also was performed. RESULTS: No serious reactions or deaths occurred in any group. The occurrence of overall minor adverse events (usually warmth, headache, taste distortion, rash) was similar for the different groups. Laboratory results showed no significant difference across groups. There was no significant difference in image quality detected among groups. CONCLUSION: There was no detectable difference in safety and imaging efficacy among the three contrast groups in this study. However, patients from the University of Wisconsin experienced significantly less injection discomfort with iodixanol-270 than with iohexol-300. Large clinical studies may more definitively determine the presence and nature of the relative advantages of iodixanol compared with currently available ionic and nonionic contrast agents.

Magnetic resonance imaging detection of extraluminal enterally administered gadopentetate dimeglumine in a rat model of intestinal ischemia.

RATIONALE AND OBJECTIVES: We assessed whether intestinal ischemia would result in transudation of orally administered gadopentetate dimeglumine into the peritoneal cavity. METHODS: Twenty-eight rats were anesthetized and midline laparotomy was performed. Animals were divided into four groups: control, ligation of a single mesenteric arcade, ligation of six consecutive arcades, and ligation of the anterior mesenteric artery (analogous to the superior mesenteric artery in humans). A 1.0-ml enteric bolus of gadopentetate dimeglumine diluted with sterile water (1:1) was given via gavage. Magnetic resonance imaging was performed 2 hr after laparotomy and reviewed for the presence of intraperitoneal gadopentetate dimeglumine by two experienced observers. Animals were sacrificed 24 hr after surgery for pathologic examination. RESULTS: Four animals died prior to sacrifice. The bladder had a grossly high signal in all cases, implying some degree of intravascular absorption of the contrast material. A correlation was found between increasing mean radiology scores and increasing numbers of ligated vessels. The intraperitoneal signal tended to be higher in experimental animals than in control animals. Histologic damage was more severe in experimental animals (ischemic changes extending deeper into the intestinal wall) than in control animals. CONCLUSION: Direct visualization of spilled gastrointestinal gadopentetate dimeglumine helped discriminate ischemic from control rats in this model.

MR hysterosalpingography in a rabbit model.

Our objective was to evaluate the efficacy of MR imaging as compared with conventional hysterosalpingography (HSG) for the detection of fallopian tube patency after uterine injection of contrast material. Rabbit uterine horns (n= 18) were catheterized transvaginally. Five fallopian tubes were ligated and 11 were left unaltered. T1-weighted gradient-echo MR images were obtained before, during, and after injection of 1.0-3.0 mL of a dilute gadolinium-containing contrast agent. Corresponding conventional studies were performed with an equivalent volume of iohexol. Images were evaluated by two blinded readers. Observers agreed in all cases on the presence (n = 11) or absence (n = 5) of peritoneal spill with conventional HSG. Interpretation of MR HSG concurred with conventional HSG in 14 of 16 cases for each observer (P > .05). Reasons for misdiagnosis included small amounts of spill (n = 2), artifact (n = 1), and subtle spill between bowel loops (n = 1). Sensitivity and specificity for MR HSG were 95.5% and 70%, respectively, for the diagnosis of tubal patency/occlusions. No statistical difference was found between MR HSG and conventional HSG for the diagnosis of fallopian tube patency/obstruction. Potential advantages of MR HSG include no ionizing radiation, potentially diminished local contrast toxicity, superior visualization of uterine fibroids and endometriosis, and visualization of ovaries. We conclude that this technique warrants further study, including the use of a primate model to better simulate human anatomy.

Pulsed magnetization transfer contrast for MR imaging with application to breast.

The relative populations and transverse relaxation times of the solid-like hydrogen pool (PB and T2B) and the magnetization transfer (MT) rates between the solid-like and liquid-like hydrogen pools (kappa) have been determined for three different agar gel concentrations (2%, 4%, and 8% by weight) as well as excised fibroglandular breast tissue specimens. PB was determined to be .003(.001), .01(.002), .02(.01), and .06(.01); T2B was determined to be 13.0(.2), 14.0(.1), 14.5(.1) and 15.2(1.3) microseconds; and kappa was determined to be 0.78(.01), 1.15(.02), 2.00(.02), and 3.55(1.5) sec-1 for the 2%, 4%, and 8% agar gels and the fibroglandular tissue, respectively. The image signal intensities of a pulsed MTC-prepared gradient-echo imaging technique are predicted using these MT parameters and are shown to agree well with experimental data obtained from a clinical MR imaging system. This technique is shown to suppress signal intensity of fibroglandular breast tissue by 40%-50% without exceeding SAR limits (< or = 8 W/kg) and is helpful for visualizing lesions and silicone implants.

Lesion visualization by targeted computed tomography liver enhancement in dogs.

RATIONALE AND OBJECTIVES: We conducted a pilot study to determine the potential advantages of using liver-specific targeted computed tomography (CT) contrast agents for lesion detection. METHODS: Eight dogs had liver infarcts created by percutaneous injections of ethanol. Each dog underwent CT scans with four imaging techniques: unenhanced, intravenous contrast enhanced (IVCE), CT arterial portography (CTAP), and targeted liver enhancement with iodipamide ethylester (IDE) particles. Lesions were assessed quantitatively to determine liver-to-lesion density differences and the drop in density across liver edge as a quantitative measure of edge sharpness. Expert readers subjectively analyzed data to determine lesion visibility and edge sharpness. RESULTS: Liver-to-lesion density differences were greatest with CTAP (56.4 +/- 35.5 Hounsfield units [H]) followed by IDE (41.1 +/- 7.0 H), i.v. (22.7 +/- 6.0 H), and unenhanced scans (13.6 +/- 4.1 H; ps < .05 for CTAP versus unenhanced and IDE versus unenhanced). Edges were best defined both subjectively and quantitatively on IDE-enhanced scans. CONCLUSION: Targeted liver-specific contrast agents have potential to increase lesion visibility when compared with standard i.v. contrast enhancement of the liver by increasing lesion edge definition and liver-to-lesion attenuation differences. Further work in animal tumor models, and clinical trials as agents become available, appears justified.

Imaging of pancreas transplants.

The pancreas transplant is difficult to monitor both clinically and by imaging. Complications such as thrombosis, infection, pancreatitis, bleeding, anastomotic leak, or rejection may quickly progress to transplant failure. Ultrasound, CT, MR imaging, fluoroscopy, nuclear scintigraphy, and angiography may be used to help define the etiology of transplant compromise; however, all have marked limitations, and none has proved to be the study of choice. The surgeon and radiologist must carefully coordinate clinical suspicion with the strengths of the various modalities to optimize a timely diagnosis.

Gadolinium-enhanced breast MRI.

The inherent overlap in the T1 and T2 relaxation of benign and malignant breast lesions has hindered progress in the application of MRI to evaluate this organ. Indeed, lesions in a glandular breast may completely blend in with normal breast tissues, a problem unenhanced MRI shares with mammography. However, infusion of intravenous Gd-DPTA accompanied by rapid MR imaging results in successful detection of most invasive breast malignancies. Inspection of the lesion morphology and enhancement profile shows that most malignancies have an irregular border, enhance very rapidly, and display a distinct early washout phase. On the other hand, fibroadenomas have a smooth or gently lobulated border and enhance in a continuous monotonic fashion. Some pitfalls exist such as the variable enhancement associated with DCIS and premenopausal breast tissue. This publication reviews the literature with respect to Gd-enhanced breast MRI, focusing on strengths and weaknesses, and suggests appropriate indications for employing this new approach to breast imaging. Patient preparation and discussion of technical parameters and tradeoffs is also addressed. The exact place of MRI in the work-up of the breast-problem patient has yet to be settled, but already MRI can help radiologists offer a more conclusive diagnosis in mammographically perplexing situations, particularly in patients with radiographically dense breasts.

Off-resonance spin locking for MR imaging.

Off-resonance spin locking is investigated as a low power method for achieving low field spin-lattice relaxation contrast using high field clinical MR imaging systems (e.g., 1.5 tesla). Spin-lattice relaxation times and equilibrium magnetizations in the off-resonance rotating frame (T1 rho(off), beta) were measured for tissue-mimicking phantom materials as a function of the ratio of the amplitude to the resonance offset of the spin-locking pulse (f1/delta). The phantom materials consisted of vegetable oil to simulate fat and two different gels containing 2% and 4% agar to simulate nonfatty tissues with different macromolecular compositions. These measurements were used to verify a signal strength equation for a multislice off-resonance spin-locking technique implemented on a clinical MR imaging system operating at 1.5 tesla. Although the oil showed little change in image contrast with increasing f1/delta, the two gels demonstrated a strong variation which provided improved discrimination compared to T1-weighted imaging. Off-resonance spin locking is suggested as a method for improving delineation of breast lesions and a preliminary clinical example from a patient volunteer is presented.

Conventional chest radiography vs dual-energy computed radiography in the detection and characterization of pulmonary nodules.

OBJECTIVE: We evaluated a single-exposure, phosphor-plate, dual-energy imaging device that produces, in addition to conventional chest radiographs, both tissue- and bone-selective images. Our purpose was to determine whether dual-energy radiography was more accurate than routine chest radiography for detection and characterization of pulmonary nodules. SUBJECTS AND METHODS: Two hundred patients undergoing chest CT were asked to volunteer to have dual-energy and conventional chest radiographs obtained immediately before or after their CT scan. Radiographs from a subset of 50 of these patients with 116 CT-detected nodules and 10 patients with normal findings on CT scans of the chest were presented to the observers for the nodule detection study. Similarly, radiographs from a subset of 29 patients with 20 calcified and 20 uncalcified nodules were presented to five observers to determine nodule calcification. Dual-energy images were produced by filtering the X-ray tube output with a gadolinium sheet while using a multiple phosphor plate receptor. A dual-energy triad of images consisting of a conventional image, a tissue-selective image, and a bone-selective image were produced. The conventional chest radiographs and dual-energy image sets were presented to observers in random order. Data from a free response receiver operating curve and a receiver operating curve were generated for nodule detection and characterization, respectively. RESULTS: By using the dual-energy images, all five observers improved their ability to diagnose pulmonary nodules (p = .0005) and to characterize nodules as calcified (p = .005). CONCLUSION: By eliminating rib shadows with tissue-selective images and enhancing calcified structures with bone-selective images, dual-energy chest radiography improved the ability of all observers, regardless of expertise, to detect and characterize pulmonary nodules.

MR imaging of adrenal lymphoma.

A case of lymphoma of the adrenal glands is presented. Both computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated large bilateral adrenal masses with no other associated abdominal abnormalities. MR was better able to demonstrate inferior vena caval patency than CT, and effectively exclude pheochromocytoma as a differential diagnostic consideration due to signal characteristics of the masses.

Ultrasonographic evaluation of renal transplantation.

Ultrasonography of the renal transplant is still a key screening examination for transplant dysfunction. The addition of Doppler technology has permitted screening for hemodynamic alterations. Ambitious researchers predicted that these hemodynamic profiles would permit the differentiation of rejection from other complicating factors; however, recent research and clinical experience has shown this to be ineffective. Imaging identification of a dilated collecting system identifies the patient population that should undergo a Whitaker procedure. Identification of large or increasing fluid collections helps focus attention to possible hemorrhage or urine leak. Similarly, the ultrasonographic identification of a lymphocele as the cause of leg edema or hydronephrosis rapidly focuses surgical treatment. Doppler evaluation of hemodynamics must be performed on all renal transplant recipients. Although the role of the resistive index in predicting rejection has been minimized lately, numerous vascular complications, if untreated, would result in loss of the kidney. Doppler sonography identifies those patients who would benefit most from renal arteriography. The evaluation of renal morphology on the basis of ultrasonography alone has little role in predicting the cause of transplant dysfunction. We continue to evaluate renal size and to correlate it with the clinical presentation as well as resistive index to defer patients from biopsy if a more obvious cause of dysfunction is identified.

Sonography of renal transplants in dogs: the effect of acute tubular necrosis, cyclosporine nephrotoxicity, and acute rejection on resistive index and renal length.

Results of studies on the accuracy of the resistive index as a predictor of acute renal transplant rejection have varied widely. Clinical evaluations are limited by the inability to control the numerous coincidental factors that affect vascular resistance. We performed a controlled study in dogs to isolate the effects of acute tubular necrosis, cyclosporine toxicity, and acute rejection on the resistive index, and to compare them with a population of normal control subjects. By doing so, we hoped to identify the patterns of change in the resistive index over time and possibly explain the wide spectrum of resistive index data reported in the literature. Resistive index, a parameter calculated from relative systolic and diastolic velocity, indicates parenchymal resistance to perfusion. Since an increase in renal length also has been reported useful in predicting rejection, we studied changes in length in each of the isolated conditions. The normal control group (four dogs) had heterotopic autotransplantation with minimal cold ischemic time. The acute tubular necrosis group (six dogs) had heterotopic autotransplantation with 1 hr of warm ischemic time. The cyclosporine toxicity group (four dogs) was allowed approximately 3 months to heal from heterotopic autotransplantation. Very high (toxic) doses of cyclosporine were then administered. The acute rejection group (five dogs) had heterotopic allografting with minimal cold ischemic time. No medications were administered. In all groups, the abnormalities induced were confirmed by biopsy. Creatinine levels were also used to monitor cyclosporine toxicity. In the normal control and acute tubular necrosis groups, resistive index increased immediately after surgery, returning to baseline within 10 days. Renal length increased slightly in both groups, but the duration of increase was longer in the acute tubular necrosis group. No significant change in resistive index or renal length was seen in the cyclosporine toxicity group. In the acute rejection group, an initial decrease in resistive index during the mild to moderate phase was followed by a rapidly progressive increase with worsening rejection. Renal length increased progressively beginning immediately after surgery. Our study determined the patterns of change in resistance and renal length over time as caused by the isolated pathologic states. Our finding that vascular resistance decreased in mild to moderate acute rejection was unexpected, since almost all the literature reports resistive index elevation. This may explain some of the conflicting results obtained in Doppler investigations of rejection. Our results on renal length reinforce the positive clinical reports of its predictive value in rejection.

MRI of the pancreas transplant: lack of correlation between imaging and clinical status.

Twenty-five MRI scans were performed on 14 patients with cadaveric pancreatic transplants to determine the role of this modality in the evaluation of transplant dysfunction. Our population included 12 normal transplants and 13 recipients with pancreatic graft dysfunction (either rejection or pancreatitis). Six of the latter patients had two or more scans permitting reassessment of the same transplant in various states of health. T1-and T2-weighted MR images were evaluated qualitatively and quantitatively to see if certain patterns were associated with clinical status. We found that although MRI was capable of producing excellent images of the in situ pancreatic transplant, this modality was unable to reliably distinguish the normal from the abnormal transplant. This conclusion differs from prior assessments; possible reasons for this are discussed.