Monitoring angiogenesis in human melanoma xenograft model using contrast-enhanced ultrasound imaging.

The potential for noninvasive monitoring and quantification of tumor angiogenesis with contrast-enhanced ultrasound imaging has been investigated in a murine cancer model. Seventy athymic nude mice were implanted with the human melanoma cell line DB-1 but only 30 of these were available for the final study. The 30 mice were divided into three groups (10 mice/group), which were studied with contrast-enhanced ultrasound imaging 4, 5 or 6 weeks post-implantation. Power Doppler and pulse inversion harmonic imaging (PIHI) were performed (in real time and intermittently) with a Sonoline Elegra scanner (Siemens Medical Solutions, Issaquah, WA) following injection of Optison (dose: 0.4-0.6 ml/kg; GE Healthcare, Princeton, NJ). Ultrasound results were compared to immunohistochemical stains for endothelial cells (CD31), vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2). Linear regression analysis indicated statistically significant correlations between the percent area stained with VEGF and ultrasound measures of tumor neovascularity obtained with all three techniques (p < 0.01). Contrast-enhanced ultrasound imaging of tumor neovascularity appears to provide a noninvasive marker of angiogenesis corresponding to the expression of VEGF in the DB-1 model and may become a useful tool for monitoring clinical anti-angiogenic therapies.

Assessment of angiogenesis: implications for ultrasound imaging.

In this paper, the fundamentals of tumor angiogenesis and the implications for ultrasound imaging will be described. Twenty-eight athymic nude mice were implanted with the human melanoma cell lines DB-1 or MW-9 (14 mice/group). Ultrasound contrast agents were injected in the tail veins. Power Doppler and pulse inversion harmonic imaging (PI-HI) was performed (in real time and intermittently). Ultrasound results were compared to immunohistochemical stains for endothelial cells (CD31), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2). Linear regression analysis indicated statistically significant correlations between percent area stained with COX-2 and with VEGF relative to power Doppler (p<0.05) and intermittent PI-HI (p<0.05) measures of tumor neovascularity in the MW-9 and the DB-1 mice, respectively. Preliminary results from a human trial of the anti-angiogenic drug Angiostatin (Entremed, Rockville, MD) showed tumor volumes increased in two patients, while the vascularity remained virtually unchanged. Conversely, in three patients with diminished tumor volumes vascularity increased by 38%. In conclusion, contrast enhanced ultrasound imaging of tumor neovascularity may provide noninvasive markers of angiogenesis and may become a useful tool for monitoring anti-angiogenic therapies in vivo.

Intraoperative sonographic localization of breast masses: success with specimen sonography and surgical bed sonography to confirm excision.

OBJECTIVE: To assess the use of intraoperative sonography for localization of breast masses at excisional biopsy, with specimen and surgical bed sonography to confirm excision. METHODS: A computer search of the 5-year period from January 1993 through January 1998 revealed 138 consecutive women referred for sonographically guided excisional biopsy of 148 masses; 35 masses were excluded because they had no postoperative mammograms. One hundred thirteen masses constituted the study group. Specimen sonography (n = 60) or surgical bed sonography (n = 53) was performed as the initial evaluation to confirm excision, but ultimately, surgical bed sonography may have been necessary after specimen sonography, and specimen sonography may have been necessary after surgical bed sonography. The miss rates determined by postoperative imaging were calculated for each group and compared with those of mammographically guided needle localization series from the literature. RESULTS: Follow-up physical examination and mammography showed no residual mass in the region of surgery in any patient. However, follow-up sonography had 1 miss in the initial specimen sonogram group (1 [1.7%] of 60) and 1 miss in the initial surgical bed group (1 [1.9%] of 53). As shown by the Fisher exact test, there was no significant difference between the miss rates of the 2 initial methods of confirming lesion excision or between the miss rates of these initial methods, both groups combined, and 6 mammographic localization series from the literature. CONCLUSION: Intraoperative breast sonography, using specimen sonography and scanning the surgical bed, has miss rates comparable with those of mammographic needle localization. Follow-up sonography must be performed if there is any doubt of complete excision.

Comparison of unenhanced and contrast-enhanced spiral CT for assessing interval change in patients with colorectal liver metastases.

RATIONALE AND OBJECTIVES: The purpose of this study was to determine whether the interval change in hepatic colorectal metastases as assessed with serial computed tomographic (CT) scans without contrast material enhancement differs from that as assessed using serial, portal dominant phase, contrast-enhanced CT scans. MATERIALS AND METHODS: Unenhanced and contrast-enhanced abdominal CT scans were obtained in 28 patients. Three radiologists separately reviewed serial unenhanced and contrast-enhanced studies to assess the interval change in liver metastases. These radiologists recorded total number of lesions, bidimensional measurements of the largest lesions (as many as three), and overall impressions regarding the interval change (none, worse, or better). RESULTS: Among the 84 judgments (28 patients x 3 radiologists), comparisons of unenhanced and contrast-enhanced CT studies were concordant in 60 assessments (71%). Nineteen (23%) showed mild disagreement. Of these, contrast-enhanced CT studies demonstrated disease stability when unenhanced CT studies demonstrated otherwise in 11 judgments, whereas unenhanced CT studies demonstrated stability when contrast-enhanced CT studies demonstrated otherwise in eight assessments. Furthermore, of the five marked disagreements, two resulted from a conclusion of interval improvement on unenhanced CT studies and a conclusion of interval worsening on contrast-enhanced CT studies, whereas three demonstrated the opposite. Neither set of serial CT studies systematically resulted in under- or overestimation of disease progression (McNemar Q test, P < .25). CONCLUSION: The authors found no consistent pattern to demonstrate that serial unenhanced or contrast-enhanced CT studies resulted in over- or underestimation of disease progression.

Indirect MR arthrography of the knee: effects of low-intensity ultrasound on the diffusion rate of intravenously administered Gd-DTPA in healthy volunteers.

RATIONALE AND OBJECTIVES: To evaluate whether application of low-intensity ultrasound may increase the diffusion rate of intravenously administered gadopentetate dimeglumine (Gd-DTPA) and increase the amount of joint fluid on indirect magnetic resonance (MR) arthrography. METHODS: Conventional MR imaging, indirect MR arthrography, and power Doppler ultrasonography were performed before and after application of therapeutic, pulsed low-intensity ultrasound in 12 asymptomatic knees of 12 volunteers. Intra-articular diffusion of intravenously administered Gd-DTPA as measured by signal intensity differences of the intra-articular joint fluid before and after ultrasound treatment was assessed. In addition, the amount of joint fluid was rated, and differences in synovial blood flow as evidenced by power Doppler ultrasonography were noted. RESULTS: All volunteers tolerated well the application of therapeutic low-intensity ultrasound. A significant increase in intra-articular diffusion of intravenously administered Gd-DTPA was noted in all knees, and an increase in joint fluid was noted in 8 of 12 knees (66.6%). Detection of power Doppler flow signal in the synovium of the suprapatellar recess was possible in one instance at posttreatment exam. CONCLUSIONS: Use of pulsed, therapeutic low-intensity ultrasound may increase the diffusion rate of intravenously administered Gd-DTPA and may induce joint effusion.

Sonographically guided renal mass biopsy: indications and efficacy.

PURPOSE: To review the clinical indications, pathologic results, and success rate of all our sonographically guided solid renal mass biopsies over a 5-year period. METHODS: Between 1993 and 1998, 44 consecutive patients underwent sonographically guided percutaneous biopsy of a solid renal mass. Indications included prior history of nonrenal malignancy, metastatic disease of unknown primary origin, previous contralateral nephrectomy for a renal cell neoplasm, a renal transplant mass, suspected renal lymphoma, history of tuberous sclerosis, and poor surgical candidacy. Aspiration biopsies were initially performed with 22- to 18-gauge spinal needles. If the initial cytologic evaluation findings were nondiagnostic, core biopsies were then performed with 20- to 18-gauge core biopsy guns. Dictated sonographic reports of the biopsies were reviewed to determine the following: indication for biopsy, location and size of the renal mass, needle gauge and type, number of needle passes, and complications. Final cytologic and surgical pathologic records were reviewed. RESULTS: Thirty-six (82%) of the 44 biopsy specimens were diagnostic. Aspirated smears were diagnostic in 24 (67%) of these cases, with the diagnosis made on the basis of cell block alone in an additional 2 (6%). A definitive diagnosis came from core biopsy alone in 10 cases (28%). The 18-gauge core needle yielded diagnostic results more reliably than the 20-gauge core needle, and a significant correlation was seen between core biopsy needle size and the rate of diagnostic core samples (P = .017). Pathologic diagnoses included renal cell carcinoma (n = 18), lymphoma (n = 4), oncocytic neoplasm (n = 4), transitional cell carcinoma (n = 2), angiomyolipoma (n = 1), papillary cortical neoplasm (n = 1), and metastatic carcinoma (n = 6). Complications were seen in 4 (9%) of 44 cases; all were treated conservatively. CONCLUSIONS: For specific clinical indications, sonographically guided fine-needle aspiration and core biopsy of a solid renal mass can be performed safely. In many cases, a definitive diagnosis can be made on the basis of fine-needle aspiration alone. However, diagnosis may ultimately require core biopsy, for which 18-gauge core needles would be more reliably diagnostic than 20-gauge needles.

Ultrasound of the ankle and foot.

Ultrasound is an excellent tool for evaluating common ankle problems. it is more economical than MRI and its real-time nature helps in correlating the study with the symptomatic area. US can be used in ankle to evaluate tendons (including tears, tendinitis and tenosynovitis), joints, plantar fascia, ligaments, soft tissue masses, ganglion cysts, Morton's neuroma, and to look for foreign bodies. Power Doppler can be used to evaluate blood flow in acute inflammatory process and in reflex sympathetic dystrophy.

Safety and efficacy of sonographically guided random core biopsy for diffuse liver disease.

Sonographic guidance is commonly used in the biopsy of focal hepatic lesions, but biopsy for diffuse disease is often non-image-guided. We evaluated the safety and efficacy of real-time sonographically guided random core biopsy in the assessment of diffuse liver disease in 210 patients. The two most common indications for biopsy were viral hepatitis (in 113 patients) and elevated liver function test results of unknown cause (in 54 patients). Ultrasonography and pathology reports were reviewed retrospectively to determine number of needle passes and final diagnoses. Adequate tissue was obtained in all 210 patients, with 259 of 269 (96%) passes having been successful. Specimens were submitted for light microscopy and other tests as indicated. No difference in success rates was found for right and left lobe biopsies. No major complications occurred. Minor complications occurred in 10 of 210 (4.8%) patients and were self-limited. Sonographically guided core liver biopsy is a safe and effective method for the diagnosis of liver disease.

Size of colorectal liver metastases at abdominal CT: comparison of precontrast and postcontrast studies.

PURPOSE: To investigate whether measurements of hepatic metastases from colorectal carcinoma before contrast material administration are significantly different statistically from measurements after contrast material administration. MATERIALS AND METHODS: Twenty-four patients with hepatic metastases from colorectal carcinoma underwent spiral computed tomography (CT) with 7-mm collimation. The liver was imaged before and in the portal-dominant phase after intravenous contrast material administration. For each scan, one to three discrete liver lesions were selected for measurement (n = 49). Three experienced radiologists performed independent measurements of the selected lesions on both pre- and postcontrast images at a computer workstation. A three-way analysis of variance (ANOVA) was performed: subjects by raters (the three independent radiologists) by pre- or postcontrast status. The dependent variable was the product of bidimensional measurements. RESULTS: Sixty-seven percent (33 of 49) of the lesions were measured as larger on precontrast images; 33% (16 of 49), as smaller. There was high interrater reliability, with an intraclass correlation coefficient greater than 0.9 ANOVA showed significant subject, rater, and contrast material effects (P < .001) for the largest lesions in each liver. Contrast material status was a significant factor for all lesion sizes (P < .003). CONCLUSION: On average, hepatic metastases from colorectal carcinoma are significantly smaller after contrast material administration.

CT assessment of abdominal hemorrhage in coagulopathic patients: impact on clinical management.

BACKGROUND: To assess how computed tomography (CT) affected clinical management in coagulopathic patients with suspected spontaneous abdominal hemorrhage. METHODS: Fifty-four patients with coagulopathy underwent CT for possible abdominal hemorrhage. Medical records were reviewed retrospectively for pre-CT management strategy, degree of clinical suspicion for abdominal hemorrhage, CT findings, and post-CT management strategy. RESULTS: Abdominopelvic CT demonstrated hemorrhage in 31/54 (57%) of patients; 20/54 (37%) of patients had retroperitoneal hemorrhage, 2/54 (4%) had hemoperitoneum, and 9/54 (17%) had hemorrhage confined to the thigh, groin, and/or abdominal wall. CT directly affected clinical management in 28/54 (54%) cases; 17/31 (55%) CT scans that were positive for hemorrhage had a clinical impact versus 11/23 (48%) negative CT scans. This difference was not statistically significant (p = 0.61). CT scans with a higher pretest suspicion for abdominal hemorrhage were more likely to have hemorrhage detected (p = 0.0046) but not more likely to have a clinical impact (p = 0.73). CONCLUSIONS: CT to assess for abdominal hemorrhage had a direct impact on clinical management in about one-half of coagulopathic patients. Positive and negative CT studies were equally likely to affect management.

Spiral CT of acute pulmonary thromboembolism: evaluation of pleuroparenchymal abnormalities.

PURPOSE: The goal of this work was to identify and categorize the spectrum of pulmonary parenchymal and pleural abnormalities identified by CT in patients with acute pulmonary thromboembolism (PE). METHOD: A review of interpretations from 4,715 consecutive contrast-enhanced thoracic CT studies identified 41 examinations in which the diagnosis of PE was reported. Thirty-four studies were available for review, and two radiologists confirmed intraluminal defects in 31 patients. The number of emboli were counted and localized using bronchopulmonary nomenclature. Associated parenchymal and pleural abnormalities were tabulated. RESULTS: Of the 31 patients, 13 underwent confirmatory or correlative studies including angiography, radionuclide study, or autopsy. In addition, deep venous thrombosis was confirmed by ultrasound or MRI in 13 patients. An average of 7.5 emboli per patient was detected. Pleuroparenchymal findings were as follows: Nine patients (29%) had no acute pulmonary parenchymal or pleural abnormality. In the remaining 22 patients, pleural effusion was the most common abnormality, found in 14 of 31 (45%). Ten patients (32%) had peripheral wedge-shaped parenchymal opacities suggestive of pulmonary infarction. Normally enhancing lobar atelectasis was seen in nine patients (29%). Six patients (19%) demonstrated heterogeneous parenchymal enhancement within nonaerated lung, two of whom had pathologically proven pulmonary infarct. Thirteen of 31 patients underwent high resolution CT; a typical mosaic perfusion pattern was seen in only 1 patient. CONCLUSION: Twenty-nine percent of patients with acute PE had no acute lung parenchymal abnormality on CT; thus, the absence of parenchymal abnormality on CT does not exclude PE. High resolution CT mosaic perfusion was not a common feature of acute pulmonary embolism. Regions of decreased enhancement within nonaerated lung, seen in 19%, may prove to be an indicator of pulmonary infarction; however, this is a nonspecific finding.

US, CT, and MR evaluation of accessory renal arteries and proximal renal arterial branches.

RATIONALE AND OBJECTIVES: The purpose of this study was to compare color Doppler ultrasound (US), computed tomographic (CT) angiography, and magnetic resonance (MR) angiography for the evaluation of accessory renal arteries and proximal branches of the main renal artery. MATERIALS AND METHODS: Fifty-six subjects who had undergone conventional arteriography of the renal arteries participated in a prospective comparison of Doppler US (45 patients), CT angiography (52 patients), and nonenhanced MR angiography (28 patients). Conventional arteriography depicted 28 accessory renal arteries and 21 proximal branches of the main renal artery within 2 cm of the aorta. RESULTS: US depicted five of 24 accessory renal arteries seen at arteriography but no proximal arterial branches. CT angiography depicted 24 of 26 accessory renal arteries and 13 of 17 proximal arterial branches, as well as 15 additional accessory renal arteries not seen at conventional arteriography. MR demonstrated 11 of 15 accessory arteries, as well as four additional accessory arteries not seen at conventional arteriography. MR did not depict any of nine proximal arterial branches seen at conventional arteriography. CONCLUSION: When compared with US or nonenhanced MR angiography, CT is the preferred method for evaluation of accessory renal arteries and proximal branches of the renal artery.

Renal artery stenosis: CT angiography--comparison of real-time volume-rendering and maximum intensity projection algorithms.

PURPOSE: To compare results of helical computed tomographic (CT) angiography with real-time interactive volume rendering (VR) to CT angiography with maximum intensity projection (MIP) for the detection of renal artery stenosis. MATERIALS AND METHODS: Twenty-five patients underwent both conventional and CT angiography of the renal arteries. Images were blindly reviewed after rendering with MIP and VR algorithms. MIP images were viewed in conjunction with axial CT images; VR models were evaluated in real time at the workstation without CT images. Findings in 50 main and 11 accessory renal arteries were categorized as normal or by degree of stenosis. RESULTS: All arteries depicted on conventional angiograms were visualized on MIP and VR images. Receiver operating characteristic (ROC) analysis for MIP and VIR images demonstrated excellent discrimination for the diagnosis of stenosis of at least 50% (area under the ROC curve, 0.96-0.99). Although sensitivity was not significantly different for VR and MIP (89% vs 94%, P > .1), specificity was greater with VR (99% vs 87%, P = .008 to .08). Stenosis of at least 50% was overestimated with CT angiography in four accessory renal arteries, but three accessory renal arteries not depicted at conventional angiography were depicted at CT angiography. CONCLUSION: In the evaluation of renal artery stenosis, CT angiography with VR is faster and more accurate than CT angiography with MIP. Accessory arteries not depicted with conventional angiography were depicted with both CT angiographic algorithms.

Clinical impact of sonographically guided biopsy of salivary gland masses and surrounding lymph nodes.

Although fine-needle aspiration biopsy of salivary gland masses has been reported in the otolaryngology literature, the use of sonography to guide the biopsy of nonpalpable masses and masses seen on other cross-sectional imaging studies has not been described. Our goal was to evaluate sonographically guided biopsy of masses and lymph nodes related to the salivary glands. We analyzed the records of 18 patients who had undergone fine-needle aspiration biopsy of a salivary gland mass or lymph node with a 25-, 22-, or 20-gauge needle. A definitive cytologic diagnosis was made for 13 of the 18 patients (72%); cytology was suggestive but not definitive in three patients (17%) and insufficient in two (11%). Definitive diagnoses were made in three cases of reactive lymph node, in two cases each of lymph node metastasis and Warthin's tumor, and in one case each of pleomorphic adenoma, adenoid-cystic carcinoma, schwannoma-neurofibroma, parotid metastasis, parotid lymphoma, and Sjögren's-related lymphoid-epithelial lesion. Sonographically guided biopsy allows for confident needle placement in masses seen on computed tomography and magnetic resonance imaging. Sonography can usually distinguish a perisalivary lymph node from true intrasalivary masses, and it can help the surgeon avoid the pitfall of a nondiagnostic aspiration of the cystic component of masses. We conclude that sonographically guided biopsy of salivary gland masses can provide a tissue diagnosis that can have a direct impact on clinical decision making.

Increased soft-tissue blood flow in patients with reflex sympathetic dystrophy of the lower extremity revealed by power Doppler sonography.

OBJECTIVE: We evaluated the ability of power Doppler sonography to show increased soft-tissue blood flow in patients with reflex sympathetic dystrophy of the lower extremity. SUBJECTS AND METHODS: Power Doppler sonography was performed in 30 patients with reflex sympathetic dystrophy of the lower extremity and in 26 asymptomatic control subjects. The bilateral power Doppler sonograms that were obtained of the soft tissues of the dorsum of the foot of each subject were grouped in pairs, and three sonologists who were unaware of clinical information independently reviewed the images. Images were evaluated for the amount of power Doppler signal shown on the following scale: 1 = no flow or minimal flow; 2 = mild flow; 3 = moderate flow; and 4 = marked flow. RESULTS: More power Doppler flow was seen in the patients with reflex sympathetic dystrophy than in the control subjects (p < .005). In addition, side-to-side asymmetry of flow was seen in patients, but this trend was not statistically significant (p < .20). Receiver operating characteristic (ROC) analysis showed that combined flow and asymmetry were more related to reflex sympathetic dystrophy than either parameter alone (area under the ROC curve: for flow, 0.748; for asymmetry, 0.566; for both, 0.799). We found that when the sum of power Doppler flow in both feet was greater than or equal to five, and asymmetry of flow was greater than or equal to one, the sensitivity of power Doppler sonography for reflex sympathetic dystrophy was 73% and the specificity was 92%. CONCLUSION: Patients with reflex sympathetic dystrophy of the lower extremity have increased power Doppler flow compared with asymptomatic control subjects. Patients may also exhibit more side-to-side asymmetry of flow than control subjects.

Comparison of Doppler US and CT angiography for evaluation of renal artery stenosis.

RATIONALE AND OBJECTIVES: The authors compared Doppler ultrasound (US) with computed tomographic (CT) angiography in the evaluation of stenosis of the main renal artery. MATERIALS AND METHODS: Fifty-six patients who had undergone conventional angiography of the renal arteries participated in a prospective comparison of Doppler US (45 patients) and CT angiography (52 patients). US evaluation included both the main renal artery and segmental renal arteries. RESULTS: There were 27 main renal arteries with at least 50% stenosis in 20 patients. In 36 patients, there was no significant stenosis. All cases of main renal artery stenosis detected with Doppler US of the segmental arteries were also identified with Doppler US of the main renal artery. The by-artery sensitivity (63%) of US of the main renal artery was greater than that (33%) of US of the segmental arteries. CT angiography was more sensitive (96%) than Doppler US (63%) in the detection of stenosis, but the specificity of CT (88%) was similar to that of US (89%). The difference in the area under the receiver operating characteristic curve (AUC) between CT (AUC = 0.94) and US (AUC = 0.82) was statistically significant (P = .038). CONCLUSION: Doppler US of the main renal artery is more sensitive than Doppler US of segmental arteries in the detection of stenosis. CT angiography is more accurate than Doppler US in the evaluation of renal artery stenosis.

Percutaneous lumbar sympathetic plexus catheter placement for short- and long-term pain relief: CT technique and results.

PURPOSE: The purpose of this work was to evaluate the use of percutaneously placed lumbar sympathetic plexus catheter placement under CT guidance in patients with complex regional pain syndrome (CRPS) or nonspecified neuropathic pain (NP) of the lower extremity. METHOD: Sixteen lumbar sympathetic plexus catheter placements were performed in seven patients with CRPS and seven patients with NP. A 19 gauge epidural catheter was placed anterior to the psoas muscle at the L2-3 level. Twenty-five to 840 mg of bupivacaine hydrochloride per day was administered for a 1 to 8 day duration. RESULTS: In CRPS patients, there was complete short-term pain relief in one patient, considerable in four, mild in one, and none in one. There was total long-term pain relief in one patient and considerable long-term pain relief in three. In three patients, there was enduring pain relief at last follow-up. In NP patients, the procedure yielded considerable short-term pain relief in four, mild in two, and none in one. There was no enduring long-term in any of these patients. A retroperitoneal abscess developed in one patient and resolved on intravenous antibiotics without sequelae. CONCLUSION: Percutaneous lumbar sympathetic plexus catheter placement is easily performed, achieves short-term pain relief in the majority of patients, and may prove effective in long-term pain relief of CRPS patients.