Andrew J. Dwyer

Functional tumor imaging with dynamic contrast-enhanced magnetic resonance imaging.

Dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) is the acquisition of serial MRI images before, during, and after the administration of an MR contrast agent. Unlike conventional enhanced MRI, which simply provides a snapshot of enhancement at one point in time, DCE‐MRI permits a fuller depiction of the wash‐in and wash‐out contrast kinetics within tumors, and thus provides insight into the nature of the bulk tissue properties. Such data is readily amenable to two‐compartment pharmacokinetic modeling from which parameters based on the rates of exchange between the compartments can be generated. These parameters can be used to generate color‐encoded images that aid in the visual assessment of tumors. DCE‐MRI is used currently to characterize masses, stage tumors, and noninvasively monitor therapy. While DCE‐MRI is in clinical use, there are also a number of limitations, including overlap between malignant and benign inflammatory tissue, failure to resolve microscopic disease, and the inconsistent predictive value of enhancement pattern with regard to clinical outcome. Current research focuses on improving understanding of the meaning of DCE‐MRI at a molecular level, evaluating macromolecular and targeted contrast agents, and combining DCE‐MRI with other physiologic imaging techniques such as positron emission tomography. Efforts to standardize DCE‐MRI acquisition, analysis, and reporting methods will allow wider dissemination of this useful functional imaging technique. J. Magn. Reson. Imaging 2003;17:509–520. Published 2003 Wiley‐Liss, Inc.

Gadolinium DTPA enhanced MR imaging of ACTH-secreting microadenomas of the pituitary gland

Gadolinium diethylenetriamine pentaacetic acid (DTPA) enhanced magnetic resonance imaging was performed in eight patients with Cushing disease and surgically proven pituitary microadenomas. A 1.5 T scanner was used with 3 mm contiguous slices. Short repetition times (TR), short echo times (TE), and long TR, long TE sequences were obtained before and serially after intravenous administration of Gd-DTPA. Three of eight (38%) microadenomas were undetectable both without and with Gd-DTPA: one post-Gd-DTPA scan was false positive on the side opposite the adenoma. Hemihypophysectomy based on a petrosal sinus adrenocorticotropic hormone (ACTH) gradient cured all three patients. Two microadenomas (25%) were visible as hypointense foci following Gd-DTPA but not on unenhanced scans. The remaining three microadenomas (38%) were seen before and after Gd-DTPA on T1-weighted images. In this small series of ACTH-producing microadenomas, one-third were seen on unenhanced 1.5 T scans, one-third were seen only after Gd-DTPA, and one-third were not imaged even with Gd-DTPA enhancement.

Magnetic resonance imaging versus computed tomography in the evaluation of soft tissue tumors of the extremities.

Twenty patients with extremity soft tissue tumors were pro- spectively evaluated with magnetic resonance imaging (MRI) and computed tomography (CT) scans with subsequent anatomic correlation of surgical findings. MRI and CT had a similar percentage of accuracy in assessing tumor relationship with major neurovascular (80% and 70%, respectively) and skeletal (80% and 75%, respectively) structures. MRI was significantly better than CT in displaying contrast between tumor and muscle when using the T2 weighted spin echo (SE) (p2 < 0.002) and inversion recovery (IR) (p2 < 0.005) pulse sequences. MRI and CT were comparable in demonstrating contrast between tumor and fat. The contrast between tumor and vessel was better displayed by MRI compared with CT when using the Tl weighted SE (p2 < 0.001) and T2 weighted SE (p2 < 0.001) pulse sequences. Tl and T2 values were measured on fresh tumor and normal tissue samples and were used to predict relative contrast on different MRI pulse sequences using isosignal contour plots. MRI appears to offer several advantages over CT in the evaluation of extremity soft tissue tumors.

Small-cell osteosarcoma

Six cases of small‐cell osteosarcoma, a tumor that resembles Ewings sarcoma but produces osteoid matrix, are presented. The patients were young (6–31 years of age) and presented with symptoms of pain and/or swelling of 1–10 months duration. The lesions demonstrated a wide variation in radiographic appearance. Histologically, the tumors were composed of small, round cells that produced variable amounts of osteoid. In three cases chondroid was also present. Two of the six patients were treated with surgery alone and four received radiation and either single‐ or multiple‐agent adjuvant chemotherapy. The two patients who received radiation and multiple‐agent adjuvant chemotherapy have no evidence of disease at four and ten years after diagnosis. Recognition of this tumor as distinct from Ewings sarcoma and from other forms of osteosarcoma is important to determine the incidence, clinical features, and optimal therapy for this tumor.

Dynamic contrast-enhanced MRI of the breast: Quantitative method for kinetic curve type assessment

OBJECTIVE The type of contrast enhancement kinetic curve (i.e., persistently enhancing, plateau, or washout) seen on dynamic contrast-enhanced MRI (DCE-MRI) of the breast is predictive of malignancy. Qualitative estimates of the type of curve are most commonly used for interpretation of DCE-MRI. The purpose of this study was to compare qualitative and quantitative methods for determining the type of contrast enhancement kinetic curve on DCE-MRI. MATERIALS AND METHODS Ninety-six patients underwent breast DCE-MRI. The type of DCE-MRI kinetic curve was assessed qualitatively by three radiologists on two occasions. For quantitative assessment, the slope of the washout curve was calculated. Kappa statistics were used to determine inter- and intraobserver agreement for the qualitative method. Matched sample tables, the McNemar test, and receiver operating characteristic (ROC) curve statistics were used to compare quantitative versus qualitative methods for establishing or excluding malignancy. RESULTS Seventy-eight lesions (77.2%) were malignant and 23 (22.8%) were benign. For the qualitative assessment, the intra- and interobserver agreement was good (kappa = 0.76-0.88), with an area under the ROC curve (AUC) of 0.73-0.77. For the quantitative method, the highest AUC was 0.87, reflecting significantly higher diagnostic accuracies compared with qualitative assessment (p < 0.01 for the difference between the two methods). CONCLUSION Quantitative assessment of the type of contrast enhancement kinetic curve on breast DCE-MRI resulted in significantly higher diagnostic performance for establishing or excluding malignancy compared with assessment based on the standard qualitative method.

Arthropathy of neonatal onset multisystem inflammatory disease (NOMID/CINCA)

BackgroundNeonatal onset multisystem inflammatory disease (NOMID), an autoinflammatory disease, is characterized by fever, chronic urticarial rash, CNS manifestations, and arthropathy. Approximately 50% of patients with NOMID have de novo missense mutations in CIAS1, which is associated with modulation of the IL-1b and apoptotic pathways. Approximately 60% of NOMID patients have prominent arthropathy, most commonly involving the knees, the cause of which remains poorly understood.ObjectiveTo more fully describe the findings of NOMID arthropathy on MRI and radiography and to provide a better understanding of the origin of the bony lesions.Materials and methodsWe imaged 20 patients with NOMID to further investigate NOMID-associated bony lesions.ResultsBony abnormalities were seen in the knees of 11/20 patients. The knee findings included enlarged, deformed femora and patellae in all and tibiae in the majority, without evidence of synovitis. Some patients had other joint involvement. Most had short stature and valgus or varus knee deformities. No association was noted between bony abnormalities and CIAS1 mutations. The abnormalities appeared to be the result of a mass-producing process. The resulting heterogeneously calcified masses appeared to originate in the physis and deformed the adjacent metaphysis and epiphysis.ConclusionThese findings suggest that the arthropathy of NOMID is the result of abnormal endochondral bone growth. Further investigation is needed to determine whether this deformity is triggered by inflammation early in development or by CIAS1 mutations causing abnormal chondrocyte apoptosis.

MR imaging of pheochromocytomas

Magnetic resonance imaging (MRI) of seven patients with pheochromocytomas demonstrable by CT was performed. Magnetic resonance imaging showed all primary pheochromocytomas, as well as metastatic lesions to the thorax, retroperitoneum, and liver. The ability to distinguish pheochromocytomas from surrounding structures without the need of an intravenous contrast agent and to provide direct coronal and sagittal images suggests that MRI may be useful in detecting and localizing these tumors.

A Phase I Study of the P-Glycoprotein Antagonist Tariquidar in Combination with Vinorelbine

Purpose: P-glycoprotein (Pgp) antagonists have had unpredictable pharmacokinetic interactions requiring reductions of chemotherapy. We report a phase I study using tariquidar (XR9576), a potent Pgp antagonist, in combination with vinorelbine. Experimental Design: Patients first received tariquidar alone to assess effects on the accumulation of 99mTc-sestamibi in tumor and normal organs and rhodamine efflux from CD56+ mononuclear cells. In the first cycle, vinorelbine pharmacokinetics was monitored after the day 1 and 8 doses without or with tariquidar. In subsequent cycles, vinorelbine was administered with tariquidar. Tariquidar pharmacokinetics was studied alone and with vinorelbine. Results: Twenty-six patients were enrolled. Vinorelbine 20 mg/m2 on day 1 and 8 was identified as the maximum tolerated dose (neutropenia). Nonhematologic grade 3/4 toxicities in 77 cycles included the following: abdominal pain (4 cycles), anorexia (2), constipation (2), fatigue (3), myalgia (2), pain (4) and dehydration, depression, diarrhea, ileus, nausea, and vomiting, (all once). A 150-mg dose of tariquidar: (1) reduced liver 99mTc-sestamibi clearance consistent with inhibition of liver Pgp; (2) increased 99mTc-sestamibi retention in a majority of tumor masses visible by 99mTc-sestamibi; and (3) blocked Pgp-mediated rhodamine efflux from CD56+ cells over the 48 hours examined. Tariquidar had no effects on vinorelbine pharmacokinetics. Vinorelbine had no effect on tariquidar pharmacokinetics. One patient with breast cancer had a minor response, and one with renal carcinoma had a partial remission. Conclusions: Tariquidar is a potent Pgp antagonist, without significant side effects and much less pharmacokinetic interaction than previous Pgp antagonists. Tariquidar offers the potential to increase drug exposure in drug-resistant cancers.

Detection of pulmonary metastases in patients with osteogenic and soft-tissue sarcomas: the superiority of CT scans compared with conventional linear tomograms using dynamic analysis.

A prospective serial evaluation in 19 patients with soft-tissue and osteogenic sarcomas was performed to determine whether computerized tomography (CT) or conventional linear tomography (LT) detected pulmonary metastases earlier. Analysis of the metastatic nodules was performed radiographically with histologic confirmation by obtaining serial CTs and LTs followed by metastasectomy. Nodules were classified as stable, growing, or developing and by detection on CT and/or LT. CT was the first positive study in a significantly greater number of patients (13 CT, 1 LT; P less than .005), and CT detected the nodules earlier than LT (56 CT first v 7 LT first; P less than .0001). Ninety of 166 nodules resected were detected by CT, LT, or both (54%). The median size of metastatic nodules documented at surgical exploration and first detected by CT was significantly smaller than that first detected by LT (7.6 mm for CT v 13.2 mm for LT; P less than .05). Of 55 histologically documented metastases detected initially either by CT or LT, CT was markedly superior to LT with 50 (91%) first detected only by CT (P less than .001). These data reveal that CT detects more pulmonary metastases earlier than LT and that developing or growing nodules in patients with sarcomas are usually metastases. Decisions regarding metastasis resection in sarcoma patients, therefore, should be based primarily on CT findings.

Computer-aided Diagnosis of Pulmonary Infections Using Texture Analysis and Support Vector Machine Classification

RATIONALE AND OBJECTIVES The purpose of this study was to develop and test a computer-assisted detection method for the identification and measurement of pulmonary abnormalities on chest computed tomographic (CT) imaging in cases of infection, such as novel H1N1 influenza. The method developed could be a potentially useful tool for classifying and quantifying pulmonary infectious disease on CT imaging. MATERIALS AND METHODS Forty chest CT examinations were studied using texture analysis and support vector machine classification to differentiate normal from abnormal lung regions on CT imaging, including 10 patients with immunohistochemistry-proven infection, 10 normal controls, and 20 patients with fibrosis. RESULTS Statistically significant differences in the receiver-operating characteristic curves for detecting abnormal regions in H1N1 infection were obtained between normal lung and regions of fibrosis, with significant differences in texture features of different infections. These differences enabled the quantification of abnormal lung volumes on CT imaging. CONCLUSION Texture analysis and support vector machine classification can distinguish between areas of abnormality in acute infection and areas of chronic fibrosis, differentiate lesions having consolidative and ground-glass appearances, and quantify those texture features to increase the precision of CT scoring as a potential tool for measuring disease progression and severity.