Non-enhancing Regions Research Articles

Perfusion, diffusion and spectroscopy values in newly diagnosed cerebral gliomas

To evaluate perfusion, diffusion, and spectroscopy values in enhancing and non-enhancing lesions for patients with newly diagnosed gliomas of different grades. Sixty-seven patients with newly diagnosed glioma were entered into the study 20 grade II, 26 grade III and 21 grade IV. MR data were acquired at 1.5T and included diffusion weighted images (59/67 patients), dynamic perfusion weighted images (30/67 patients) and 3D H-1 MR spectroscopy (64/67 patients). Enhancing and non-enhancing lesions were delineated by a neuroradiologist and applied to maps of relative cerebral blood volume (rCBV), apparent diffusion coefficient (ADC), relative anisotropy (RA) and metabolite intensities. The median rCBV within enhancing regions of grade IV gliomas was significantly elevated relative to enhancing regions in grade III gliomas and normal brain. ADC was elevated relative to normal brain, but was not significantly different between grades or between enhancing and non-enhancing regions. The RA was higher in the non-enhancing region of grade IV gliomas relative to grade II and grade III. Levels of lactate plus lipid were significantly elevated in grade IV relative to grade II and grade III gliomas. Both enhancing and non-enhancing regions in grade IV gliomas showed significant correlations between CBV, ADC and choline levels. The data were consistent with grade IV gliomas having higher membrane turnover, increased cell density and increased vascularity within enhancing lesions. Analysis of the correlations among parameters within grade IV gliomas suggested that high vascularity (high rCBV) was correlated with increased cellularity (low ADC) and increased membrane turnover (high choline) in these lesions. The non-enhancing region of grades II and III gliomas had MR parameters consistent with increased cellularity and/or membrane turnover.

Is There a Role for Apparent Diffusion Coefficients in the Differential Diagnosis of Brain Tumors?

We determined the potential benefits of apparent diffusion coefficient (ADC) values of enhancing-nonenhancing solid portions, cystic-necrotic areas and surrounding edema in the differential diagnosis of brain tumors. Eighty-eight patients with brain tumors: 16 low-grade gliomas, 21 high-grade gliomas, 26 metastases and 25 meningiomas were imaged prospectively in a 1.5 Tesla magnetic resonance (MR) unit. Routine MR imaging and echo-planar diffusion-weighted imaging (DWI) with b values of 0 and 1000 mm(2)/s were performed. ADC values were obtained in different tumor parts and peritumoral edema. The ADCs of contrast-enhancing tumor regions were higher in high-grade gliomas than meningiomas (p<0.05). No significant differences were found in ADCs of contrast-enhancing regions comparing other tumor groups (p≥0.05). The ADCs in non-enhancing tumor regions did not differ between low-grade and high-grade gliomas (p≥0.05). The ADCs in cystic-necrotic regions of tumors and surrounding edema were not significantly different comparing all tumor groups (p≥0.05). There were no significant differences between ADCs of contrast-enhancing and non-enhancing regions of high-grade and low-grade gliomas (p≥0.05). No significant differences were found in ADCs of contrast-enhancing and non-enhancing areas of tumors comparing to surrounding edema (p≥0.05). ADC was not found to be useful in distinguishing different tumor types and its value in the diagnosis of brain tumors is limited due to considerable overlaps.

Contrast-enhanced sonography of pancreatic carcinoma: correlations with pathological findings

We examined contrast-enhanced harmonic gray-scale sonographic findings of pancreatic carcinoma in relation to the pathological findings in resected specimens to evaluate correlations between observations made by this modality and the pathological findings. The pathological findings of surgical specimens obtained from 16 patients were examined in relation to the contrast-enhanced harmonic gray-scale sonography findings. Lesion vascularity was examined by contrast-enhanced harmonic gray-scale sonography from 20 to 50 s after the injection of Levovist (Schering, Berlin, Germany) (early phase), and lesion enhancement was also monitored at approximately 90 s after injection (delayed phase). Contrast-enhanced harmonic gray-scale sonography showed positive enhancement in 12 of the 16 lesions (peripheral tumor region alone, n = 9; entire tumor, n = 3), while the other 4 lesions showed no contrast enhancement in any region. Twelve enhanced regions (9 peripheral tumor region and 3 entire tumor regions) detected by contrast-enhanced harmonic gray-scale sonography showed: (1) mild fibrosis with inflammation, in 10 regions (83%); (2) the presence of both carcinoma cells and residual acinar cells in 8 (67%); and (3) presence of relatively large arteries in 2 (17%). In contrast, 13 non-enhanced regions (4 entire tumor regions and 9 central regions) showed: (1) severe fibrosis in 10 regions (77%); (2) necrosis in 7 (54%); and (3) mucin in 4 (31%). Contrast-enhanced harmonic gray-scale sonographic findings of pancreatic carcinoma are influenced by interstitial histological features associated with tumor growth.

Medullomyoblastoma: a radiographic and clinicopathologic analysis of six cases and review of the literature.

Medullomyoblastoma (MMB) is a rare cerebellar embryonal neoplasm that occurs almost exclusively in children. It is biphasic by microscopy, containing myoblastic and primitive neuroectodermal components. The authors conducted a retrospective review of the radiographic and pathologic characteristics, treatment, and clinical outcomes of six children with MMB who were treated at St. Jude Children's Research Hospital (Memphis, TN) between 1984 and 2003. Fluorescence in situ hybridization (FISH) data were available for four children. A literature review also was conducted and focused on imaging and pathologic findings. The median age at diagnosis was 4.5 years (range, 0.83-7.5 years). Radiographically, all tumors were cerebellar and exhibited variable enhancement, and 50% of tumors had necrotic foci. Three tumors contained discrete, magnetic resonance imaging (MRI) T2-weighted-hypointense/computed tomography (CT)-hyperdense enhancing regions and separate hyperintense/hypodense nonenhancing regions, which correlated microscopically with geographic islands of primitive neuroectodermal and rhabdomyoblastic cells. Large cell/anaplastic (five tumors), nodular/desmoplastic (two tumors), and classic (two tumors) medulloblastoma histologies were encountered either alone (five tumors) or in combination with each other (two tumors). All 4 tumors that were tested exhibited alterations in chromosome 17 or c-myc amplification. All patients underwent macroscopic total resection and subsequently received chemotherapy and craniospinal (five patients) or local conformal (one patient) radiotherapy. At a median follow-up of 92 months (range, 23-187 months), 3 patients remain alive with no evidence of disease, 2 patients have died of disease, and 1 patient has died of secondary acute lymphocytic leukemia. The results of the current study demonstrated the frequent correlation of biphasic nodularity (as determined by MRI or CT) with discrete rhabdomyoblastic and primitive neuroectodermal islands (as revealed by microscopy) in MMB. These results also support the view that MMB and medulloblastoma may have common tumorigenic origins, given their similar histologic and molecular features.

Magnetic resonance image-guided proteomics of human glioblastoma multiforme.

To investigate the correlation between gadolinium contrast-enhancement patterns on T1-weighted magnetic resonance (MR) images and spatial changes in protein expression profiles in human glioblastoma multiforme (GBM) and the use of imaging as a noninvasive technique to evaluate the heterogeneity of solid tumors prior to microarray analysis. Four patients with MR images and confirmed diagnosis of GBM were enrolled in the study. Intraoperative stereotaxy was used in conjunction with MR images to identify contrast-enhanced (CE) and nonenhanced (NE) regions of the tumor during surgical resection. Total protein was extracted from resected tumor samples using standard techniques and subjected to proteomic analysis using surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS). We found that protein profiles from CE and NE regions within a given tumor have qualitative and semiquantitative proteomic pattern differences, suggesting an altered gene expression profile that correlates with detectable tissue imaging parameters. We also found that CE regions within the same tumor exhibited distinct differences in protein expression profiles, despite similar histological features. In addition, there were marked similarities in the proteomic patterns among the NE regions across all patients, while the CE regions were distinct, suggesting that the CE regions have complex protein profiles unique to individuals. The results demonstrate that major differences in protein expression patterns within a tumor can be correlated to radiographic findings. Image-guided proteomics holds promise for characterizing tissue prior to microarray analysis designed to identify specific diagnostic markers and therapeutic targets within solid tumors.

Comparing genomic and histologic correlations to radiographic changes in tumors: a murine SCC VII model Study 1

Rationale and Objectives. To investigate the correlation between the temporal changes in T1- and T2-weighted contrast-enhanced magnetic resonance imaging (MRI), histologic evaluation, and genomic analysis using oligonucleotide microarrays in a murine squamous cell carcinoma tumor models Materials and Methods. The squamous cell carcinoma (SCC VII) cell line was used to initiate subcutaneous tumors in mice. This mouse model has been used as a model for human head and neck carcinomas. Animals were imaged using contrast enhanced MRI (CE-MRI). Different stages of tumor growth were defined based on changes in the T1- and T2-weighted MRI patterns. The contrast enhancing (CE) and nonenhancing (NE) regions of the tumors were marked and biopsied for oligonucleotide microarray and histologic analysis. Tumors with no differential contrast enhancement were used as controls. Results. Distinct temporal stages of tumor progression can be defined using both T1- and T2-weighted CE-MRI and microarray analysis. The early stage tumors show a homogeneous contrast enhancement pattern in the T1- and T2-weighted images with no significant differential gene expression from the center and periphery of the tumor. The more advanced tumors that show discrete regions of contrast enhancement in the post-contrast T1-weighted MRIs and tissues from the CE and NE regions show distinctly differential gene expression profiles. Histologic analysis (hematoxylin-eosin stain) showed that the samples obtained from the periphery and center of the early stage tumors and the CE and NE regions from these more advanced tumors were similar. The gene expression profiles of late-stage tumors that showed changes in T2-weighted MRI signal intensity were consistent with tissue degradation in the NE region, which also showed characteristic signs of tissue necrosis in histologic analysis. Conclusion. These results show that temporal changes in T1- and T2-weighted CE-MRI are related to distinct gene expression profiles, and histologic analysis may not be sufficient to detect these detailed changes. As tumors progress, discrete regions of post-contrast T1 enhancement are identified; these regions have distinct gene expression patterns despite similar histologic features. In late-stage tumors, regions of T2 signal changes are observed which correspond with tissue necrosis.

Functional genomics guided with MR imaging: mouse tumor model study.

To gain a better understanding of gene expression patterns in tumors, the authors used contrast material-enhanced magnetic resonance (MR) imaging to noninvasively characterize regions within the same tumor to provide a correlate for genomic analysis. Gene expression profiles of samples from a mouse tumor model obtained from contrast-enhanced and nonenhanced regions within the same tumor were compared with MR imaging and functional genomics. From these samples, 11000 genes were analyzed: 10 genes were up-regulated in the contrast-enhanced areas, and one gene was up-regulated in the nonenhanced regions. Several of these genes encode extracellular matrix proteins. Findings in this study demonstrate that MR imaging can serve as a powerful noninvasive tool for characterizing different regions of tumors to guide genomic analysis with high spatial and temporal resolution.

Significant antitumor effect of intratumoral ethanol injection on renal cell carcinoma.

The effects of intratumoral ethanol injection on renal cell carcinoma (RCC) heterotransplanted in nude rats were evaluated. The OUR95AF human RCC cell line was inoculated subcutaneously into the backs of nude rats. Four weeks after transplantation, the size of tumors became 1.5-2.0 cm in maximal length, and 95% ethanol was injected intratumorally once a week for five weeks. The effectiveness of this treatment was evaluated by measurement of tumor volume, magnetic resonance (MR) imaging using Gadopentetate-diethylenetriaminepentaacetic acid (Gd-DTPA) and histological examinations. In the ethanol injected group, no increase in tumor volume was recognized. The growth of the tumors was significantly suppressed after the third injection. Non-enhanced parts in MR imaging were observed in the central region of the tumors at the second injection, and increased at the third injection. After the fifth injection, only small parts of non-enhanced regions remained. Degenerative necrosis was histologically found in the non-enhanced parts of the MR image. The signal to noise ratio (SNR) and the contrast to noise ratio (CNR) calculated from T1 weighted imaging using Gd-DTPA, and relative enhancement (RE) were thought to be good parameters for evaluating the effect of ethanol injections. Intratumoral ethanol injection was very effective against RCC. Five weekly injections of ethanol induced necrosis of the tumor. MR imaging using Gd-DTPA may be a useful method for evaluating the effect of ethanol injection.

Acute pancreatitis

Both CT and sonography are useful in imaging of patients with acute pancreatitis (Table 1). Contrast-enhanced CT identifies pancreatic necrosis as intraglandular non-enhancing regions. These patients require prophylactic antibiotics. CT can identify complications and guide intervention when appropriate. All patients, even alcoholics, with acute pancreatitis, require sonography, to detect gallstones and biliary obstruction. Understanding sonographic findings in acute pancreatitis can allow diagnosis in clinically unsuspected cases. In an unpublished retrospective study, we found abnormalities in 94% of patients with acute pancreatitis. Common abnormalities include glandular heterogeneity (60%), peripancreatic and retroperitoneal inflammation (60%), and focal hypoechoic abnormalities (25%). The pancreas is diffusely hypoechoic in less than 50% of patients. Pancreatic enlargement in acute pancreatitis is probably almost universal, but difficult to judge, as pre-pancreatitis size is usually unknown and varies widely. We use 22 mm as the normal upper limit AP measurement of the pancreatic body at the level of the SMA. Acute pancreatitis-associated fluid collections are frequent and evanescent. Fluid collections that persist for 6 weeks are called pseudocysts. Table 1. Imaging in acute pancreatitis ultrasound: 1) detect gallstones as a cause of acute pancreatitis (ALL first-time patients); 2) detect bile duct dilatation and obstruction; 3) diagnose unsuspected acute pancreatitis; 4) follow known fluid collections; 5) guide aspiration and drainage CT; 6) confirm uncertain diagnosis of acute pancreatitis; 7) detect pancreatic necrosis (patients with suspected severe pancreatitis); 8) detect other complications of acute pancreatitis; and 9) guide aspiration and drainage.

Histopathological validation of a three-dimensional magnetic resonance spectroscopy index as a predictor of tumor presence.

Data obtained preoperatively from three-dimensional (3D)/proton magnetic resonance (MR) spectroscopy were compared with the results of histopathological assays of tissue biopsies obtained during surgery to verify the sensitivity and specificity of a choline-containing compound-N-acetylaspartate index (CNI) used to distinguish tumor from nontumorous tissue within T2-hyperintense and contrast-enhancing lesions of patients with untreated gliomas. The information gleaned from the biopsy correlation study was used to test the hypothesis that there is metabolically active tumor in nonenhancing regions of the T2-hyperintense lesion that can be detected using MR spectroscopy. Patients suspected of harboring a glioma underwent 3D MR spectroscopy during their preoperative MR imaging examination. Surgical navigation techniques were used to record the location of tissue biopsies collected during open resection of the tumor. A receiver operating curve analysis of the CNI and histological characteristics of specimens at each biopsy location was performed to determine the optimal threshold of the CNI required to separate tumor from nontumorous tissue. Histograms of the CNIs within enhancing and nonenhancing regions of lesions appearing on MR images were generated to determine the spatial distribution of CNIs consistent with tumor. Biopsy samples containing tumor were distinguished from those containing a mixture of normal, edematous, gliotic, and necrotic tissue with 90% sensitivity and 86% specificity by using a CNI threshold of 2.5. The CNIs of nontumorous specimens were significantly different from those of biopsy specimens containing Grade II (p < 0.03), Grade III (p < 0.005), and Grade IV (p < 0.01) tumors. On average, one third to one half of the T2-hyperintense lesion outside the contrast-enhancing lesion contained CNI greater than 2.5.

Nonenhancing tissue on MR imaging of pedal infection: characterization of necrotic tissue and associated limitations for diagnosis of osteomyelitis and abscess.

We studied the frequency, location, extent, and signal characteristics of nonenhancing tissue in pedal infections and correlated those areas with surgical and histologic findings. One hundred ten contrast-enhanced 1.5-T MR imaging foot examinations in 102 patients (28 women, 74 men; mean age, 59 years), 82% of whom had diabetes mellitus, were reviewed by two musculoskeletal radiologists for the presence of areas without recognizable enhancement. The number, size, location, signal characteristics, and enhancement ratio of nonenhancing regions were noted. MR imaging findings were compared with surgical and histology reports. Nonenhancing regions were found in 27 feet (24.5%, 96.3% in diabetic patients, p = 0.032) at the forefoot (n = 16), toes (n = 8), and heel (n = 3). The mean size of the nonenhancing regions was 4.1 x 2.7 x 1.4 cm. Signal characteristics on T1-weighted images were isointense to muscle (n = 21, 77.8%), hypointense to muscle (n = 3, 11.1%), heterogeneous (n = 2, 7.4%), and isointense to fat (n = 1, 3.7%). On T2-weighted images, the signal was hyperintense to muscle (n = 12, 44.4%), heterogeneous to muscle (n = 9, 33.3%), equal to fluid (n = 3, 11.1%), and hypointense to muscle (n = 3, 11.1%). The mean signal increase after contrast administration was 3.57% for observer 1 and 2.68% for observer 2. Necrotic tissue was surgically confirmed in the nonenhancing areas in 26 feet (96.3%). Five abscesses and three cases of osteomyelitis were misdiagnosed on MR images because of lack of enhancement. Nonenhancing areas are seen in one fourth of pedal infections, occur almost exclusively in diabetic patients, and represent necrotic tissue. Only contrast-enhanced images allow reliable recognition of these regions. Lack of enhancement in these areas can mask the presence of abscess and osteomyelitis.

Percutaneous radiofrequency ablation therapy with combined angiography and computed tomography assistance for patients with hepatocellular carcinoma.

Radiofrequency ablation (RFA) for patients with hepatocellular carcinoma (HCC) has been reported previously. This technique is superior to percutaneous microwave coagulation therapy (PMCT) for the enlargement of the necrotic area. Therefore, a few treatment sessions of RFA for patients with small HCC lesions measuring < 3 cm in greatest dimension can achieve complete necrosis. To achieve this with a one-treatment RFA session, the authors designed the technique of RFA with angiography combined with computed tomography (angio-CT) assistance. The advantages of this technique are that it is possible to detect small satellite nodules and to evaluate the real-time therapeutic effect immediately after RFA. Ten patients with 12 HCC lesions measuring < 4 cm in greatest dimension underwent RFA with angio-CT assistance. The authors performed standard RFA for six patients (seven tumors) and RFA with balloon occlusion of the hepatic artery (balloon-occluded RFA [BoRFA]) for four patients (five tumors). Final therapeutic efficacy was evaluated with dynamic CT scans performed 2 weeks after treatment. On CT arteriography (CTA) obtained immediately after treatment, a hyperattenuating ring around the nonenhanced region was apparent in all patients. On CT scans obtained 2 weeks after treatment, this ring disappeared, and the greatest dimension of the nonenhanced region was slightly larger than that on the CTA obtained immediately after treatment. The authors achieved complete eradication with one treatment session of RFA in 8 of 10 patients (80%). Local recurrence occurred in one patient 10 months after treatment. The greatest dimension of the area coagulated by BoRFA was significantly larger (greatest long-axis dimension, 38.2 +/- 2.8 mm; greatest short-axis dimension, 35.0 +/- 1.7 mm; n = 5 lesions) than without it (greatest long-axis dimension, 30.0 +/- 4.1 mm; greatest short-axis dimension, 27.0 +/- 4.3 mm; n = 4 lesions; greatest long-axis dimension, P = 0.009; greatest short-axis dimension, P = 0.006). No major complications occurred in any patient. The authors were able to achieve success with a single treatment session in patients with small HCC using RFA with angio-CT assistance. They consider that RFA with angio-CT assistance is a safe and effective technique for the treatment of patients with small HCC.

Treatment of intrahepatic malignancy with radiofrequency ablation

BACKGROUND Radiofrequency (RF)-induced tissue coagulation represents a new approach for the thermal destruction of tumors within the liver. The purpose of the current study was to 1) assess technique safety; 2) determine the extent and evolution of induced cellular damage; and 3) correlate the observed pathologic effects with radiologic studies. METHODS Twenty-three tumors measuring ≤ 8 cm (19 colorectal metastases and 4 hepatomas) in 22 patients were treated with RF (range, 500–1550 milliamperes) using internally cooled electrodes. All treated tumors were resected to allow pathologic analysis. Eleven tumors were treated intraoperatively under ultrasonographic guidance and excised immediately. Twelve tumors were treated percutaneously using ultrasound or computed tomography (CT) guidance and subsequently were excised 3–7 days after ablation. Contrast-enhanced CT (n = 12) and magnetic resonance imaging (MRI) (n = 2) were performed after ablation of all percutaneously treated patients. RESULTS Tumors treated intraoperatively did not demonstrate definitive coagulative necrosis. However, pathologic abnormalities suggestive of tissue injury were observed with hematoxylin and eosin staining, and absent cytosolic and mitochondrial enzyme activity suggested irreversible cellular damage. In contrast, specimens removed > 3 days after ablation showed definite, contiguous coagulative necrosis without intervening areas of viable tumor. CT and MRI scans demonstrated circumscribed hypodense, nonenhancing regions surrounding the electrode tract as early as 15 minutes after ablation. These corresponded within 2 mm to measurements of coagulation at pathology. CONCLUSIONS RF ablation is a minimally invasive and safe approach to the treatment of tumors in the liver. Tumors treated with RF energy do not immediately demonstrate coagulative necrosis, but do show evidence of irreversible cellular damage. The extent of tumor necrosis correlates closely with findings at contrast-enhanced imaging. Cancer 2000;88:2452–63. © 2000 American Cancer Society.

Treatment of intrahepatic malignancy with radiofrequency ablation

Radiofrequency (RF)-induced tissue coagulation represents a new approach for the thermal destruction of tumors within the liver. The purpose of the current study was to 1) assess technique safety; 2) determine the extent and evolution of induced cellular damage; and 3) correlate the observed pathologic effects with radiologic studies. Twenty-three tumors measuring </= 8 cm (19 colorectal metastases and 4 hepatomas) in 22 patients were treated with RF (range, 500-1550 milliamperes) using internally cooled electrodes. All treated tumors were resected to allow pathologic analysis. Eleven tumors were treated intraoperatively under ultrasonographic guidance and excised immediately. Twelve tumors were treated percutaneously using ultrasound or computed tomography (CT) guidance and subsequently were excised 3-7 days after ablation. Contrast-enhanced CT (n = 12) and magnetic resonance imaging (MRI) (n = 2) were performed after ablation of all percutaneously treated patients. Tumors treated intraoperatively did not demonstrate definitive coagulative necrosis. However, pathologic abnormalities suggestive of tissue injury were observed with hematoxylin and eosin staining, and absent cytosolic and mitochondrial enzyme activity suggested irreversible cellular damage. In contrast, specimens removed > 3 days after ablation showed definite, contiguous coagulative necrosis without intervening areas of viable tumor. CT and MRI scans demonstrated circumscribed hypodense, nonenhancing regions surrounding the electrode tract as early as 15 minutes after ablation. These corresponded within 2 mm to measurements of coagulation at pathology. RF ablation is a minimally invasive and safe approach to the treatment of tumors in the liver. Tumors treated with RF energy do not immediately demonstrate coagulative necrosis, but do show evidence of irreversible cellular damage. The extent of tumor necrosis correlates closely with findings at contrast-enhanced imaging.

Model-Updated Image-Guided Neurosurgery: Preliminary Analysis Using Intraoperative MR.

In this paper, initial clinical data from an intraoperative MR system are compared to calculations made by a three-dimensional finite element model of brain deformation. The preoperative and intraoperative MR data was collected on a patient undergoing a resection of an astrocytoma, grade 3 with non-enhancing and enhancing regions. The image volumes were co-registered and cortical displacements as well as subsurface structure movements were measured retrospectively. These data were then compared to model predictions undergoing intraoperative conditions of gravity and simulated tumor decompression. Computed results demonstrate that gravity and decompression effects account for approximately 40% and 30%, respectively, totaling a 70% recovery of shifting structures with the model. The results also suggest that a non-uniform decompressive stress distribution may be present during tumor resection. Based on this preliminary experience, model predictions constrained by intraoperative surface data appear to be a promising avenue for correcting brain shift during surgery. However, additional clinical cases where volumetric intraoperative MR data is available are needed to improve the understanding of tissue mechanics during resection.

Radio-frequency-induced coagulation necrosis in rabbits: immediate detection at US with a synthetic microsphere contrast agent.

To determine whether a synthetic ultrasonographic (US) contrast agent can be used to differentiate coagulation necrosis from untreated tumor immediately after radio-frequency ablative therapy. VX2 (adenocarcinoma) tumors (0.8-1.5-cm diameter) were implanted into 12 rabbits. Gray-scale and color Doppler US were performed with or without intravenous injection of a US contrast agent composed of poly-lactide-co-glycolic acid polymeric (PLGA) microspheres (2-micron diameter) filled with perfluorocarbon gas. Radio frequency was applied to each nodule for 6 minutes at 127 mA +/- 33 (mean +/- SD) (tip temperature, 92 degrees C +/- 2). Repeat US with a second dose of the contrast agent was performed immediately after ablation. In four animals, a third dose was administered 30-120 minutes after ablation. Radiologic-histopathologic correlation was performed and included in vivo staining and studies of mitochondrial function. Intense contrast agent enhancement was seen throughout the tumor prior to ablation. At gray-scale US, ablation produced hyperechoic foci, which were within 1 mm of the foci identified at histopathologic examination in seven of 12 animals (58%). After the administration of contrast material, foci devoid of previously visualized enhancement, which measured 7.3-15.0 mm, were identified. These were within 1 mm of the size of the foci identified at histopathologic examination in 11 of 12 animals (92%, P < .01). In two animals, enhancement depicted viable tumor, which appeared hyperechoic, on nonenhanced images. On delayed images, hyperechoic areas decreased in size, whereas the nonenhanced region remained unchanged. A PLGA microspherical US contrast agent enabled the immediate detection of coagulation necrosis as a region devoid of contrast enhancement after radio-frequency ablation in rabbit hepatic tumors. Therefore, this agent could provide real-time guidance during complex ablative procedures and may provide an efficient technique for postprocedural assessment.

FIBROUS HISTIOCYTOMA AND FIBROUS TISSUE TUMORS OF THE ORBIT

Fibrous orbital tumors present clinically and radiographically in a broad spectrum ranging from a benign mass, to locally aggressive tumor, to invasive malignancy. Pathologic analysis and diagnosis are often challenging, usually based on a combination of light microscopy, immunohistochemistry, and electron microscopic findings. Some light microscopic and immunohistochemical findings, however, are relatively characteristic. A storiform or cartwheel pattern and vimentin staining are characteristic of fibrous histiocytoma. A herringbone pattern is usually found in fibrosarcoma. A "patternless pattern" and CD34 staining is found most commonly in solitary fibrous tumor. CT and MR imaging findings, as well as clinical presentation, in fibrous orbital lesions are often difficult to distinguish from those of other orbital masses, although there may be useful clues. Benign fibrous lesions are usually well-circumscribed and may chronically remodel bone, whereas more aggressive malignant fibrous tumors tend to have infiltrating margins and may destroy bone on CT or MR imaging. With malignant fibrous masses, enhancement patterns on CT or MR imaging may be more inhomogeneous, with avascular or necrotic nonenhancing regions. At MR imaging, benign lesions tend to be homogeneous on T1, T2, and postgadolinium T1-weighted images, whereas malignant soft tissue lesions may change their pattern from homogeneous on T1-weighted images to heterogeneous with low signal septations on T2-weighted images. Low T2 signal comprising part or all of a fibrous lesion correlates with dense collagen fibers, with a less cellular matrix. Areas of hyperintensity on T2-weighted images correspond with a more cellular matrix of fibroblasts and other cells. Calcification within a tumor, however, may give a similar appearance. Thus, if a lesion has predominantly low signal on T2-weighted images, or less specifically has low signal septations, then a fibrous orbital lesion with high collagen content may be ranked higher in the differential diagnosis (see Figs. 2E and 3B). When T2 signal is intermediate-to-high, then one has a difficult time narrowing the differential diagnosis. Radiographically, distinguishing these lesions from other fibrous orbital lesions, as well as from other varieties of orbital masses, is difficult. Differential diagnosis of fibrous orbital masses includes all the fibrous lesions described in this article, in addition to schwannoma (Fig. 7), neurofibroma (Figs. 4 and 8), hemangiopericytoma (Figs. 9 and 10), rhabdomyosarcoma, meningioma, lymphoma, and metastasis (Figs. 11 and 12). A history of prior orbital irradiation for retinoblastoma or other tumors may raise the possibility of radiation-induced secondary tumors, such as MFH, fibrosarcoma, and osteosarcoma. Determining the extent of orbital involvement remains the primary goal of the radiologist. The final diagnosis still rests with the pathologist.

Accuracy of CT in estimating extent of pancreatic necrosis

The objective of this study was to determine whether nonenhancing pancreatic lesions are accurate in estimating pancreatic necrosis. Twenty-six consecutive abdominal computed tomography (CT) examinations performed over a 3-year period that met the CT criteria for pancreatic necrosis were reviewed. Follow-up CTs in three of 26 patients demonstrated pancreatic enhancement, indicating viable parenchyma, within the previously nonenhancing regions. All three patients had undergone surgical debridement in that area. Twenty-three cases demonstrated either no change or enlargement of the nonenhancing pancreatic lesions. Follow-up ranged from 1 week to 26 months. While CT is accurate in diagnosing pancreatic necrosis, lack of enhancement in CT may occasionally overestimate the extent of necrosis. Nonenhancing, viable but at-risk tissue may be present adjacent to frankly necrotic tissue. Surgical debridement may facilitate recovery of this viable tissue, which may enhance normally on follow-up CT.

Serial proton magnetic resonance spectroscopy imaging of glioblastoma multiforme after brachytherapy.

The utility of three-dimensional (3-D) proton magnetic resonance spectroscopy (1H-MRS) imaging for detecting metabolic changes after brain tumor therapy was assessed in a serial study of 58 total examinations of 12 patients with glioblastoma multiforme (GBM) who received brachytherapy. Individual proton spectra from the 3-D array of spectra encompassing the lesion showed dramatic differences in spectral patterns indicative of radiation necrosis, recurrent or residual tumor, or normal brain. The 1H-MRS imaging data demonstrated significant differences between suspected residual or recurrent tumor and contrast-enhancing radiation-induced necrosis. Regions of abnormally high choline (Cho) levels, consistent with viable tumor, were detected beyond the regions of contrast enhancement for all 12 gliomas. Changes in the serial 1H-MRS imaging data were observed, reflecting an altered metabolism following treatment. These changes included the significant reduction in Cho levels after therapy, indicating the transformation of tumor to necrotic tissue. For patients who demonstrated subsequent clinical progression, an increase in Cho levels was observed in regions that previously appeared either normal or necrotic. Several patients showed regional variations in response to brachytherapy as evaluated by 1H-MRS imaging. This study demonstrates the potential of noninvasive 3-D 1H-MRS imaging to discriminate between the formation of contrast-enhancing radiation necrosis and residual or recurrent tumor following brachytherapy. This modality may also allow better definition of tumor extent prior to brachytherapy by detecting the presence of abnormnal metabolite levels in nonenhancing regions of solid tumor.

Temporal characteristics of radiosurgical lesions in an animal model.

To characterize the temporal course of radiosurgical lesions, 19 cats were irradiated in an animal linear accelerator radiosurgical device. The animals were followed clinically and, at 3.5, 6, 12, 18, 23, 29, and 63 weeks, were studied with gadolinium-enhanced magnetic resonance (MR) imaging. They were then sacrificed after Evans blue dye perfusion, and gross pathological and histopathological studies were performed. Mild neurological deficits developed between 3.5 and 4.5 weeks, correlating with the onset of mass effect both grossly and radiographically and with the maximum amount of white matter edema on T2-weighted MR imaging and microscopic examination. Clinical improvement occurred within several weeks as these resolved. The lesions were of similar size at all time intervals. Gadolinium-enhanced MR imaging demonstrated lesions with peripheral areas of enhancement and central nonenhancing regions which correlated histologically with areas of vascular proliferation and radiation necrosis, respectively. In the early lesions at 3.5 and 6 weeks, necrosis and edema were predominant. From 12 to 29 weeks, an intermediate stage was observed, with resorption of the necrotic debris as evidenced by progressive cavitation and microglial response and by increased perilesional vascularity. At 63 weeks, resorption was still taking place, but gliosis and diminution of the vascular response were seen.