Contrast-enhanced MR imaging of two superparamagnetic RES-contrast agents: functional assessment of experimental radiation-induced liver injury.

The purpose of this study was to compare liver contrast-enhancing characteristics of two superparamagnetic reticuloendothelial system (RES)-directed agents with different particle sizes, polycrystalline iron oxide nanocompounds (PION) and carboxydextran-coated maghemite (DDM128N/389, later referred to as DDM128), in an experimental model of focal radiation-induced hepatitis. PION, for the small particle size (31 nm), and DDM128, for the large particle size (59 nm), RES-directed agents were compared for liver enhancement after radiation-induced liver injury. A single x-irradiation exposure varying from 10 to 60 Gy was delivered to one side of the liver. T2-weighted spinecho magnetic resonance imaging was performed 3 days after x-irradiation at 30 minutes post-contrast. Using the RES-directed PION, the normal, non-irradiated portion of the liver decreased in signal intensity with a maximum negative enhancement of -66%, while the irradiated portion of the liver decreased in signal intensity by -24% (60 Gy). The signal intensity decline of irradiated liver tissue using PION was dose dependent, but was found at all radiation dose levels (10-60 Gy). The difference in signal intensity between irradiated (-63%) and non-irradiated (-82%) portions was also statistically different using DDM128 at 60 Gy. However, lower irradiation doses (10 and 30 Gy) failed to produce a statistically significantly different enhancement in the irradiated and non-irradiated portion of the liver. Sensitivity of liver enhancement with RES-directed agents is size dependent. The smaller particle (PION) is more sensitive for detection of radiation-induced hepatitis than the larger particle (DDM128). The relative insensitivity of DDM128 enhancement for diffuse liver injury will be clinically advantageous for detecting focal lesions in the presence of diffuse hepatic injury.

A MRI spatial mapping technique for microvascular permeability and tissue blood volume based on macromolecular contrast agent distribution.

A rapid and automated method for two-dimensional spatial depiction (mapping) of quantitative physiological tissue characteristics derived from contrast enhanced MR imaging was developed and tested in disease models of cancer, inflammation, and myocardial reperfusion injury. Specifically, an established two-compartment kinetic model of unidirectional mass transport was implemented on a pixel-by-pixel basis to generate maps of tissue permeability surface area product (PS) and fractional blood volume (BV) based on dynamic MRI intensity data after administration of albumin-(Gd-DTPA)30, a prototype macromolecular contrast medium (MMCM) designed for blood pool enhancement. Maps of PS and BV in disease models of adenocarcinoma, intramuscular abscess inflammation, and myocardial reperfusion injury clearly depicted zones of increased permeability (up to approximately 500 microl/cc/h--compared to <25 microl/cc/h in normal tissues). As revealed on PS maps, the rank ordering of studied permeability abnormalities was reperfusion injury > inflammation > tumors. A rapid, automated mapping technique derived from dynamic contrast-enhanced MRI data can be used to facilitate the identification and characterization of pathophysiologic abnormalities, specifically relative increases in blood volume and/or microvascular permeability.

Mammary carcinoma model: correlation of macromolecular contrast-enhanced MR imaging characterizations of tumor microvasculature and histologic capillary density.

PURPOSE: To determine the relationship between capillary density, a recognized surrogate of tumor angiogenesis, and magnetic resonance (MR) imaging-derived estimates of plasma volume (PV) and microvascular permeability in two mammary carcinoma models. MATERIALS AND METHODS: Dynamic spin-echo imaging was performed by using albumin-(gadolinium-diethylenetriaminepentaacetic acid)34, a prototype blood-pool contrast medium, in 14 rats with a subcutaneously implanted slow- or fast-growing subtype of R3230 mammary carcinoma. Data were fitted to an established two-compartment kinetic model to estimate PV and permeability. RESULTS: MR imaging-derived tumor PVs and permeabilities increased exponentially with increasing capillary density. MR imaging-derived microvascular characteristics correlated strongly with histologic capillary density, with an r2 of .85. CONCLUSION: Contrast medium-enhanced MR imaging may prove useful in estimating angiogenic activity in carcinomas. MR imaging may be superior to histologic assay because it is noninvasive, can be used to "sample" the entire tumor, and reflects both anatomic and physiologic characteristics.

Contrast-enhanced MR imaging assessment of tumor capillary permeability: effect of irradiation on delivery of chemotherapy.

PURPOSE: To assess the effect of x rays on tumor capillary permeability with macromolecular contrast medium (MMCM)-enhanced magnetic resonance (MR) imaging. MATERIALS AND METHODS: One of paired R3230 mammary adenocarcinomas implanted in the flanks of 48 Fischer rats was treated with a single 5- or 15-Gy dose of x rays. After 1 or 3 days, MR imaging in 30 rats was performed unenhanced and enhanced with albumin-(gadolinium diethylenetriaminepentaacetic acid)30 (0.02 mmol gadolinium per kilogram body weight). Signal intensity enhancement was analyzed to estimate fractional blood volume and permeability-surface area product (PS). In 18 irradiated rats, 2.5 mg/kg cisplatin was injected intravenously, and fractional tumor platinum concentrations were measured spectrometrically. RESULTS: MR imaging showed highest capillary permeability 1 day after 15 Gy (PS 110% above control [P<.001]); PS was elevated 57% 1 day after 5 Gy and 63% 3 days after 15 Gy (P<.05). The largest mean tumor platinum fraction occurred 1 day after 15 Gy: 48% versus 20% (control)(P<.05). CONCLUSION: Transient irradiation-induced increase in tumor capillary permeability to cisplatin can be quantified with MMCM-enhanced MR imaging.

Contrast enhancement in experimental radiation-induced liver injury: comparison of hepatocellular and reticuloendothelial particulate contrast agents.

We compared the liver enhancement of two superparamagnetic agents, polycrystalline iron oxide nanoparticles (PION) and PION coated with asialofetuin (ASF), in an experimental model of focal radiation-induced hepatitis. PION, a reticuloendothelial system-directed agent, and PION-ASF, a hepatocellular-directed agent, were compared for time-dependent liver enhancement in an experimental model of radiation-induced liver injury. Using the reticuloendothelial system (RES)-directed PION, the normal, nonirradiated portion of the liver decreased in signal intensity (SI) with a mean negative enhancement of -66% +/- 4, whereas the irradiated portion (60 Gy, 3 days before imaging) of the liver decreased in SI by -24% +/- 2, significantly less (P <.05). SI changes in irradiated liver tissue using PION were dose-dependent, being more pronounced with lower radiation exposure. The difference in SI changes induced by PION-ASF between irradiated and nonirradiated liver was not statistically different, but SI decreased with a mean negative enhancement of -80% +/- 2. The RES-directed PION is more sensitive for the detection of radiation-induced hepatitis than is the hepatocyte-directed PION-ASF. The insensitivity of PION-ASF enhancement for diffuse liver injury may be clinically advantageous for detecting focal lesions in the presence of diffuse hepatic injury.

MRI mapping of microvascular permeability and tissue blood volume.

A quick and automated method for quantitative spatial mapping of tissue characteristics derived from contrast enhanced MR imaging by a macromolecular contrast medium (MMCM) was used in normal rats. Specifically, an established two compartment unidirectional flow kinetic model was automatically implemented on a pixel by pixel basis to calculate permeability surface area product (PS) and tissue fractional blood volume (BV) from MRI dynamic intensity data. The utility of PS and BV maps were evaluated in the normal rat abdomen where a range of fractional BV was found: from 100% in the vena cava to 1% in skeletal muscles, with intermediate values for liver and kidney. Tissue permeability depicted on the PS maps was generally low for normal tissues.

Quantification of liver blood volume: comparison of ultra short TI inversion recovery echo planar imaging (ULSTIR-EPI), with dynamic 3D-gradient recalled echo imaging.

An ultra-short TI inversion recovery echo-planar imaging (ULSTIR-EPI) sequence was designed to reduce the influence of water exchange on fractional tissue blood volume (BV) estimation by measurement of T1-changes induced by a gadolinium-based macromolecular contrast medium (MMCM). Fractional liver BV in rats, estimated by ULSTIR-EPI was compared for accuracy to a fast T1-weighted three-dimensional gradient-echo (3D-SPGR, 3D-spoiled gradient recalled acquisition in a steady state) sequence using an in vitro inductively coupled plasma atomic emission spectroscopy (ICP-AES) assay for BV as a standard. Liver images for fractional BV estimation were acquired in eight rats using both ULSTIR-EPI and 3D-SPGR before and after (within 3 to 12 min) intravenous bolus administration of albumin-Gd-DTPA30 (0.05 mmol Gd/kg). Whereas both MR techniques may be useful for fractional tissue BV estimation, ULSTIR-EPI offers certain advantages including greater accuracy, direct T1 maps, and minimization of transendothelial proton exchange effects. 3D-SPGR imaging offers better spatial resolution, current availability on standard clinical MR systems, and acceptable accuracy.

Motility disorders of the esophagus: diagnosis with barium-rice administration.

PURPOSE: To evaluate the role of barium-rice administration for a standardized diagnosis of dysphagia and esophageal motility disorders. MATERIALS AND METHODS: Sixty healthy volunteers and 218 patients with various esophageal disorders (achalasia, scleroderma and other connective tissue diseases, neurologic diseases, esophagitis and others) were examined both by a conventional barium study and by a barium-rice study. The barium-rice meal consisted of barium sulfate and boiled rice, mixed half and half. The time required for esophageal clearance of one sip was measured. RESULTS: Normal esophageal transit time in healthy controls was between 5 and 15 s for both methods. In patients, the conventional barium study revealed a prolonged transit time in only 16.5% (36 of the 218 cases). The barium-rice study was abnormal in 51.8% (113 of 218 cases), independent of the underlying disease. The barium-rice study was pathological in 77 of those 182 patients (42.3%) who had normal barium transit time. In 24 patients the radiologic results was confirmed by endoscopy and manometric measurements. CONCLUSIONS: Esophageal motility abnormalities are detected by a barium-rice study with a high sensitivity. With this simple and low-cost method, quantitative and reproducible results can be obtained. Barium-rice administration is a suitable tool for screening and follow-up of patients with dysphagia and esophageal motility disorders.

Tumor angiography using high-resolution, three-dimensional magnetic resonance imaging: comparison of gadopentetate dimeglumine and a macromolecular blood-pool contrast agent.

RATIONALE AND OBJECTIVES: We compared the peritumoral vascular definition in rats using either a paramagnetic extracellular or a macromolecular contrast medium in combination with high-resolution magnetic resonance (MR) imaging. METHODS: High-resolution, three-dimensional spoiled gradient-refocused acquisition in a steady state (SPGR) images were acquired from tumor-bearing Fischer-344 rats before, immediately after, and again 40 min after administration of gadopentetate dimeglumine (0.1 mmol Gd/kg; n = 10) and albumin-(Gd-DTPA)30 (0.05 mmol Gd/kg; n = 5). Small peritumoral vessels were analyzed semiquantitatively on maximum intensity projection angiograms using a 4-point scoring system; quantitative analyses included signal-to-background ratios (SBRs) and signal-to-noise ratios. RESULTS: Gadopentetate dimeglumine caused a transient and low-scoring (0.2 +/- 0.1, SBR = 1.9 +/- 0.2) vessel definition but strong rim enhancement (score = 1.4 +/- 0.2). Albumin-(Gd-DTPA)30 produced persistent, high-quality angiograms (score = 2.6 +/- 0.2, SBR = 7.4 +/- 0.2) but minimal rim enhancement (score = 0.3 +/- 0.2). CONCLUSION: Albumin-(Gd-DTPA)30 combined with high-resolution MR imaging produces time-persistent, detailed angiographic definition of peritumoral vessels. Vascular maps obtained with gadopentetate dimeglumine enhancement are not time persistent or of equal quality.

Angiographic properties of Gd-DTPA-24-cascade-polymer--a new macromolecular MR contrast agent.

PURPOSE: A new macromolecular MR contrast agent, Gd-DTPA-24-cascade-polymer, was assessed for MR angiography of peritumoral vessels in rats. MATERIAL AND METHODS: High resolution 3D-SPGR (TR/TE 100/5ms, alpha = 90 degrees) angiograms were acquired in 10 Fischer rats bearing subcutaneous R3230 mammary adenocarcinomas. MRI was performed before, immediately and 40 min after administration of Gd-DTPA (0.1 mmol Gd/kg), and after either Gd-DTPA-cascade-polymer or albumin-(Gd-DTPA)30 (each 0.05 mmol Gd/kg). A semi-quantitative analysis of small peritumoral vessels and tumor rim enhancement was performed on maximum intensity projection (MIP) angiograms using a 4-point scoring system. A quantitative analysis compared vascular signal-to-background-(S/B), signal-to-noise-, and contrast-to-noise-ratio. RESULTS: Gd-DTPA produced a transient and low-scoring vessel definition (0.2 +/- 0.1), but strong rim enhancement (score 1.7 +/- 0.1). The cascade polymer resulted in better but submaximal vessel delineation (score 1.6 +/- 0.3, S/B 5.0 +/- 0.2) and strong rim enhancement (score 1.8 +/- 0.1). Albumin-(Gd-DTPA)30 produced the best and most time-persistent angiograms (score 2.6 +/- 0.2, S/B 7.4 +/- 0.2), but minimal rim enhancement (score 0.3 +/- 0.2). CONCLUSIONS: The Gd-DTPA-24-cascade-polymer demonstrated the useful combination of strong tumor rim enhancement and detailed angiographic definition of peritumoral vessels. These are advantages associated with extracellular and blood pool contrast media, respectively.

[Conventional roentgen diagnosis of esophageal carcinoma--a determination of current status]. / Konventionelle Röntgendiagnostik des Osophaguskarzinoms--eine Standortbestimmung.

Conventional radiological methods in the diagnosis of esophageal carcinoma include esophagography as well as chest radiography, the latter revealing pathological findings in advanced cases. Esophagography may be used for early diagnosis, tumor staging and for follow-up examinations after irradiation and/or surgery. In particular early tumor diagnosis requires a double contrast technique with an optimal mucosal coating and distension of the esophagus. The esophagogram reveals indirect signs related to the staging from the localization and length of the tumor and from ulcerations and fistulas. In the diagnosis of recurrent tumor after surgery, esophagography is not the primary diagnostic tool. After irradiation therapy, however, it can detect intramurally growing remaining or recurrent tumor.

[Pulmonary manifestations in HIV patients: role of thoracic radiography, CT and HRCT]. / Pulmonale Manifestationen bei HIV-Patienten: Rolle von Thoraxübersicht, CT und HRCT.

AIM: To determine the prevalence of pulmonary changes on chest radiographs and computed tomography (CT/HRCT) in HIV patients and their relation to pulmonary symptoms. MATERIAL AND METHOD: 64 HIV patients were examined prospectively. 15 had no respiratory symptoms (group I), 30 had non-specific respiratory symptoms (group II), 19 complained of dyspnoea (group III). Chest radiographs and CT were performed within a week. In patients with positive findings, bronchoscopy was carried out with bacteriological and histological examinations. RESULTS: In group 1, 13% of chest radiographs and 40% of CTs showed infiltrative changes. In group II, the figures were 27% and 57% respectively. In group III, abnormalities were found in all cases by both examinations. CONCLUSIONS: In the absence of pulmonary symptoms, imaging is not indicated since it has no clinical consequences. In the presence of pulmonary symptoms, CT/HRCT should be performed whether the chest radiograph is normal or not, since it may reveal additional information.

[Spiral computerized tomography of the pulmonary arteries: diagnosis of acute and chronic lung embolism]. / Spiralcomputertomographie der Pulmonalarterien: Diagnostik der akuten und chronischen Lungenembolie.

The use of tailored acquisition spiral CT protocols together with standardized contrast medium injections result in a detailed visualization of the pulmonary arteries. Since spiral CT is a quick and noninvasive imaging modality, it is especially suited for severely ill patients suspected to be suffering from acute pulmonary embolism. In contrast to perfusion scintigraphy, spiral CT will directly visualize the emboli, and should be performed if scintigraphy is not conclusive before the patient is referred to angiography. In cases of chronic pulmonary embolism spiral CT will directly visualize thromboemboli, consecutive wall thickening, pulmonary infarctions, and relative hyperperfusion as well as signs of pulmonary arterial hypertension and right heart failure. Acquisition protocols, diagnostic criteria, and clinical value of spiral CT are presented.

[CT compared with SPECT in chronic recurrent pulmonary embolism: hyperdensities as signs of pulmonary artery hyperperfusion?]. / CT im Vergleich mit SPECT bei chronisch rezidivierender Lungenembolie: Hyperdensien als Zeichen pulmonalarterieller Hyperperfusion?

UNLABELLED: Purpose of this study was to assess the aetiology of inhomogeneous lung parenchymal attenuation in patients with chronic pulmonary thromboembolism, presenting as sharply demarcated areas of increased and decreased density on computed tomography. MATERIAL AND METHODS: In 52 patients with chronic pulmonary thromboembolism, computed tomography (CT) was compared with perfusion scintigraphy (including SPECT) and agreement was assessed: "good" (all hyperdense CT segments are perfused on scan), "moderate" or "poor" (one or two resp. three or more hyperdense CT segments are not perfused). RESULTS: 44 of the 52 patients showed an inhomogeneous pulmonary attenuation on CT. Correlation of hyperdense areas with perfused lung parenchyma was graded as "good" in 26 cases, "moderate" in 14 and "poor" in 4 cases. In 40 of these 44 patients, scintigraphy revealed additional perfusion defects in homogeneously lucent areas on CT. In 6 of 8 patients with entirely homogeneous lung density on CT, SPECT revealed perfusion defects. CONCLUSION: In patients with chronic pulmonary thromboembolism, increased lung density on CT is caused by hyperperfused lung parenchyma distally to patent pulmonary arteries. SPECT proves to be more sensitive in diagnosing perfusion inhomogeneities.

Spiral CT of bronchial arteries in chronic thromboembolism.

OBJECTIVE: Computed tomography study of bronchial artery anatomy and evaluation of dilatation and tortuousity as indicators for pulmonary hypertension and surgical risk in patients with chronic thromboembolism were performed. MATERIALS AND METHODS: We retrospectively reviewed contrast-enhanced, thin section spiral CT scans of 39 patients undergoing pulmonary thromboendarterectomy. Findings were compared with mean pulmonary artery (PA) pressure in all, postoperative mortality in 33, and postoperative CT in 5 patients. Twenty patients without pulmonary hypertension served as controls. RESULTS: In the pulmonary hypertension group, 50 bronchial arteries were observed in 30 of 39 patients. Their prevalence was significantly higher than in the control group (p < 0.0001). Their proximal diameter measured > or = 1.5 mm in 20 patients (51%); a tortuous course was found in 14 (36%). The correlation between total bronchial artery diameter and mean PA pressure was poor (r = 0.2). Patients with dilated bronchial arteries had a significantly lower risk for postoperative death than patients without (p < 0.05); positive predictive value was 100% and confidence interval 0.79-1.0. Despite normal postoperative PA pressures, bronchial arteries were still visible on follow-up studies. CONCLUSION: The CT depiction of bronchial arteries, dilatation, and tortuousity provides indicators for chronic thromboembolic pulmonary hypertension. Its degree cannot be estimated. Dilated bronchial arteries are a significant predictor for survival of pulmonary thromboendarterectomy.