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Biomedical subjects

Arthur C Fleischer

Publications and source records attributed to Arthur C Fleischer.

At least 19 recordsLinked to original sources
PubMed2006

Phase I/pilot study of SU5416 (semaxinib) in combination with irinotecan/bolus 5-FU/LV (IFL) in patients with metastatic colorectal cancer.

OBJECTIVES: Determine the toxicity, tolerability, and pharmacokinetics of SU5416, a vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, coadministered with bolus 5-fluorouracil (5-FU), leucovorin, and irinotecan (IFL) in untreated patients with metastatic colorectal cancer. METHODS: SU5416 (85 or 145 mg/m2) was administered twice weekly throughout a 6-week period along with standard IFL (4 weeks on/2 weeks off). Plasma samples were assayed for SU5416, irinotecan, and SN-38 by reverse-phase HPLC. Contrast enhanced, color Doppler sonography was performed on patients at the MTD to identify changes in tumor perfusion. RESULTS: Eleven patients received treatment with SU5416 85 mg/m2 (n = 5) or 145 mg/m2 (n = 6). At 85 mg/m2, no DLTs were observed. At 145 mg/m2, grade 3 diarrhea and vomiting were observed during cycle 1; other grade 3 toxicities included fatigue, nausea, anorexia, anemia, pain, urinary retention, and hypertension. The pharmacokinetics of irinotecan and SN-38 were not altered by coadministration of SU5416. SU5416 pharmacokinetics were not altered by IFL. Contrast-enhanced, color Doppler sonography was performed on 2 patients and demonstrated reduced tumor perfusion after treatment in a patient who responded to treatment and increased perfusion in a patient who developed progressive disease. Three patients (27%) had confirmed partial responses, 2 patients (18%) had unconfirmed partial responses, and 4 patients (36%) had stable disease. CONCLUSIONS: Twice weekly SU5416 can be administered with bolus IFL without unexpected toxicities or altering the pharmacokinetic behavior of the administered drugs. Changes in tumor blood perfusion can be detected by contrast-enhanced, color Doppler sonography. The further development of SU5416 was halted before this study was completed.

Aged↗
PubMed2006

Three-dimensional sonography of the endometrium and adjacent myometrium: preliminary observations.

OBJECTIVE: By evaluating a series of patients undergoing pelvic sonography with routine 2-dimensional (2D) as well as 3-dimensional (3D) reconstructed images in the coronal plane, we attempted to characterize the types of additional information that can be obtained. METHODS: Ninety randomly selected patients undergoing transvaginal pelvic sonography were imaged according to a standard 2D protocol. A 3D uterine volume was then acquired in the sagittal plane and reconstructed in the coronal plane. The endometrium and surrounding myometrium were evaluated for architecture, masses, the relationship of masses to the endometrial cavity, and the anatomic configuration of the cavity. RESULTS: Ninety-one studies were obtained. Additional findings were obtained on the coronal view in 28 studies (30.8%). No additional findings were obtained in 63 studies (69.2%). Normal endometrial and myometrial findings were obtained by conventional 2D imaging in 42 of 91 patients. Of this group, additional findings were shown in 2 (5%) patients. Forty-nine of the 91 patients had abnormal findings by 2D imaging. Additional information was obtained in 26 (53%) of these patients. Added information included uterine anomalies, better definition of the endometrium, more accurate delineation and location of endometrial polyps, location of leiomyomas, visualization of cystic areas within the myometrium, and confirmation of the location of intrauterine devices. CONCLUSIONS: The 3D reconstructed view of the endometrium and adjacent myometrium appears to be most helpful after a conventional transvaginal study, showing abnormalities within the endometrium and myometrium but being of little added benefit if the conventional findings are normal.

Endometrium↗
PubMed2006

Noninvasive assessment of tumor vasculature response to radiation-mediated, vasculature-targeted therapy using quantified power Doppler sonography: implications for improvement of therapy schedules.

OBJECTIVE: Stereotactic radiotherapy (ablative radiation) is a modality that holds considerable promise for effective treatment of intracranial and extracranial malignancies. Although tumor vasculature is relatively resistant to small fractionated doses of ionizing radiation, large ablative doses of ionizing radiation lead to effective demise of the tumor vasculature. The purpose of this study was (1) to noninvasively monitor and compare tumor physiologic parameters in response to ablative radiation treatments and (2) to use these noninvasive parameters to optimize the schedule of administration of radiation therapy. METHODS: Lewis lung carcinoma tumors were implanted into C57BL/6 mice and treated with ablative radiation. The kinetics of change in physiologic parameters of a response to single-dose 20-Gy treatments was measured. Parameters studied included tumor blood flow, apoptosis, and proliferation rates. Serial tumor sections were stained to correlate noninvasive Doppler assessment of tumor blood flow with microvasculature histologic findings. RESULTS: A single administration of 20 Gy led to an incomplete tumor vascular response, with subsequent recovery of tumor blood flow within 4 days after treatment. Sustained reduction of tumor blood flow by administering the successive ablative radiation treatment before tumor blood flow recovery led to a 3-fold tumor growth delay. The difference in tumor volumes at each measurement time point (every 2 days) was statistically significant (P=.016). CONCLUSIONS: This study suggests a rational design of schedule optimization for radiation-mediated, vasculature-directed treatments guided by noninvasive assessment of tumor blood flow levels to ultimately improve the tumor response.

Animals↗
PubMed2006

Sonographic quantification of ovarian tumor vascularity.

OBJECTIVE: The purpose of this study was to assess the diagnostic accuracy of quantitated color Doppler sonography in differentiating benign from malignant ovarian tumors, with the use of tumor histologic examination as a reference standard. METHODS: The vascularity of 38 ovarian masses (30 benign and 8 malignant) as quantitatively depicted with color Doppler sonography was analyzed with a readily available software program (ImageJ; National Institutes of Health, Bethesda, MD). The following quantitative sonographic criteria for tumor vascularity were analyzed: the vascularity index (VI) quantified the difference between the total number of pixels and the number of pixels containing no color/totalx100, whereas the power-weighted pixel density (PWPD) weighted the strength of the signal/total. The accuracy of sonographic criteria for malignant ovarian tumors was evaluated with univariate analysis. Results of tumor histologic examination were used as proof of the final diagnosis. RESULTS: The mean values of VI and PWPD were significantly different in benign versus malignant ovarian lesions (VI, 1.3+/-1.6 versus 4.7+/-3.9; P<.01; PWPD, 2338+/-3305 versus 9403+/-9946; P<.05). With a VI of greater than 2.3, sensitivity of 75% and specificity of 90% were obtained. When combined with a PWPD of greater than 4555, sensitivity improved to 88%, and specificity improved to 93%. Morphologic analysis had sensitivity of 72% and specificity of 76% for malignancies. CONCLUSIONS: Quantitated color Doppler sonography was found to be helpful for distinguishing benign from malignant ovarian masses. However, the wide range in values makes it most useful as an adjunct to morphologic assessment. It is anticipated that quantitated color Doppler sonography could result in a slight improvement in detection of ovarian malignancies.

Female↗
PubMed2006

Correlation between estimates of tumor perfusion from microbubble contrast-enhanced sonography and dynamic contrast-enhanced magnetic resonance imaging.

OBJECTIVE: We compared measurements of tumor perfusion from microbubble contrast-enhanced sonography (MCES) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in an animal tumor model. METHODS: Seven mice were implanted with Lewis lung carcinoma cells on their hind limbs and imaged 14 days later with a Philips 5- to 7-MHz sonography system (Philips Medical Systems, Andover, MA) and a Varian 7.0-T MRI system (Varian, Inc, Palo Alto, CA). For sonographic imaging 100 microL of a perfluoropropane microbubble contrast agent (Definity; Bristol-Myers Squibb Medical Imaging, Billerica, MA) was injected and allowed to reach a pseudo steady state, after which a high-mechanical index pulse was delivered to destroy the microbubbles within the field of view, and the replenishment of the microbubbles was imaged for 30 to 60 seconds. The MRI included acquisition of a T(10) map and 35 serial T(1)-weighted images (repetition time, 100 milliseconds; echo time, 3.1 milliseconds; alpha, 30 degrees ) after the injection of 100 microL of 0.2-mmol/kg gadopentetate dimeglumine (Magnevist; Berlex, Wayne, NJ). Region-of-interest and voxel-by-voxel analyses of both data sets were performed; microbubble contrast-enhanced sonography returned estimates of microvessel cross-sectional area, microbubble velocity, and mean blood flow, whereas DCE-MRI returned estimates of a perfusion-permeability index and the extravascular extracellular volume fraction. RESULTS: Comparing similar regions of tumor tissue seen on sonography and MRI, region-of-interest analyses revealed a strong (r(2) = 0.57) and significant relationship (P < .002) between the estimates of perfusion obtained by the two modalities. CONCLUSIONS: Microbubble contrast-enhanced sonography can effectively depict intratumoral heterogeneity in preclinical xenograft models when voxel-by-voxel analysis is performed, and this analysis correlates with similar DCE-MRI measurements.

Animals↗
PubMed2005

Clarifying the role of three-dimensional transvaginal sonography in reproductive medicine: an evidenced-based appraisal.

This overview describes and illustrates the clinical applications of three-dimensional transvaginal sonography in reproductive medicine. Its main applications include assessment of uterine anomalies, intrauterine pathology, tubal patency, polycystic ovaries, ovarian follicular monitoring and endometrial receptivity. It is also useful for detailed evaluation of failed and/or ectopic pregnancy. Three-dimensional color Doppler sonography provides enhanced depiction of uterine, endometrial, and ovarian vascularity.

Journal Article↗
PubMed2005

Recent advances in the sonographic assessment of vascularity and blood flow in gynecologic conditions.

OBJECTIVE: This overview presents recent advances in sonographic depiction of vascularity and blood flow in the uterus, ovaries, and breasts. Enhanced sonographic visualization and evaluation of intraorgan vascularity has resulted from improved image processing and display. Future advances, such as the use of contrast enhancement, are also mentioned in this overview as one of many topics for future investigation. STUDY DESIGN: This is an overview of the topic based on review of the literature and the authors' experience. RESULTS: Specifically, the sensitivity of color Doppler sonography has been enhanced with the use of amplitude or power Doppler techniques. Spatial depiction of vascularity has improved because of 3-dimensional and "live 3-dimensional" processing. CONCLUSION: The combination of more sensitive color Doppler sonography and 3-dimensional imaging provides both anatomic and physiologic assessment of the vascularity and blood flow of the ovary, uterus, and breast.

Blood Vessels↗
PubMed2005

The sonographic diagnosis of adenomyosis.

Adenomyosis is a common but under-diagnosed gynecologic condition due to hypertrophied myometrial smooth muscle containing ectopic endometrial glands that is associated with pelvic pain, menorrhagia, and an enlarged uterus. This is an overview of the sonographic and magnetic resonance imaging features that have been developed in the diagnosis of adenomyosis emphasizing sonography as the initial study performed in the symptomatic patient. These features include myometrial heterogeneity, asymmetric thickening of myometrium, cysts, linear striations, and an ill-defined endometrium. Both magnetic resonance imaging and sonography can now diagnose adenomyosis with a high degree of accuracy so that treatment may be instituted specific to the disease process.

Diagnosis, Differential↗
PubMed2005

Sonography for deep venous thrombosis: current and future applications.

Deep venous thrombosis (DVT) is a one of the most common problems facing the clinician in medicine today. It is often asymptomatic and goes undiagnosed with potentially fatal consequences. Ultrasound has become the "gold standard" in the diagnosis of deep venous thrombosis and with proper attention to technique sensitivity of this test is approximately 97%. An understanding of anatomy, pathophysiology, and risk factors is important. Thrombus formation usually begins beneath a valve leaflet below the knee. Approximately 40% will resolve spontaneously, 40% will become organized, and 20% will propagate. Whether or not a calf vein thrombus is identified, a repeat examination in 7 to 10 days is recommended in patients with risk factors or when deep venous thrombosis is suspected. The three main risk factors for thrombus formation are age greater than 75 years, previous history of deep venous thrombosis, and underlying malignancy. Other diagnostic studies include the contrast venogram, CT or MRI venogram, Tc99m Apcitide study, and the laboratory test D-Dimer. The D-Dimer study is being used more frequently as a screening test with 99% sensitivity in detecting thrombus, whether deep venous thrombosis or pulmonary embolism. However, specificity is only approximately 50% with many conditions leading to false-positive exams. Therefore, a negative examination is useful in avoiding other diagnostic studies, but a positive one may be misleading. Conditions that can lead to a false-positive examination include, but are not limited to diabetes, pregnancy, liver disease, heart conditions, recent surgery, and some gastrointestinal diseases. Like the sonogram, two negative D-Dimer studies a week apart exclude the diagnosis of deep venous thrombosis. Compression sonography with color Doppler remains the best overall test for deep venous thrombosis. It is easy to perform, less expensive than most "high tech" studies, can be performed as a portable examination, and is highly reliable when done properly.

Aged↗
PubMed2005

Color Doppler sonography in obstetrics and gynecology.

This review aims to provide the reader with an overview of the present and future clinical applications in color Doppler sonography for the evaluation of vascularity and blood flow within the uterus (both gravid and nongravid), ovaries, fetus and placenta. The clinical use of color Doppler sonography has been demonstrated within many organ systems. Color Doppler sonography has become an integral part of cardiovascular imaging. Significant improvements have recently occurred, improving the visualization and evaluation of intra-organ vascularity, resulting from enhancements in delineation of tissue detail through electronic compounding and harmonics, as well as enhancements in signal processing of frequency- and/or amplitude-based color Doppler sonography. Spatial representation of vascularity can be improved by utilizing 3D and 4D (live 3D) processing. Greater sensitivity of color Doppler sonography to macro- and microvascular flow has provided improved anatomic and physiologic assessment throughout pregnancy and for pelvic organs. The potential use of contrast enhancement is also mentioned as a means to further differentiate benign from malignant ovarian lesions. The rapid development of these new sonographic techniques will continue to enlarge the scope of clinical applications in a variety of obstetric and gynecologic disorders.

Female↗
PubMed2005

Sonographic depiction of intratumoral vascularity with 2- and 3-dimensional color Doppler techniques.

OBJECTIVE: The purpose of this study was to describe patterns seen on 2- and 3-dimensional color Doppler sonographic depiction of intratumoral vessels and to correlate these patterns to histopathologic findings in an attempt to assess their clinical importance. METHODS: We conducted a retrospective analysis of 26 patients with ovarian masses and intratumoral abnormalities in whom standard 2- and 3-dimensional color Doppler sonography was performed. RESULTS: Two- and 3-dimensional color Doppler sonography depicted several patterns of vascularity within ovarian masses. These included masses with vascularity confined to the wall or loculus and those with central versus peripheral vascularity. The presence of central intratumoral vascularity had a high positive predictive value (90%) for malignancy. Conversely, the absence of intratumoral vascularity had a high negative predictive value (96%). CONCLUSIONS: Three-dimensional color Doppler sonography is helpful in depicting overall vessel density and branching patterns within an intratumoral abnormality. This technique seems to be useful in distinguishing benign from malignant ovarian masses.

Female↗
PubMed2005

Sonographic depiction of changes of tumor vascularity in response to various therapies.

PURPOSE: To evaluate the diagnostic accuracy of power Doppler sonography for the depiction of changes in tumor vascularity with various therapeutic regimens. MATERIALS AND METHODS: Tumor cells were implanted subcutaneously in thirty-two mice and assigned to four treatment groups: control, radiation therapy, antiangiogenesis therapy (VEGF [vascular endothelial growth factor] receptor antagonist, SU11248), or combined antiangiogenesis and radiation therapy. Twenty of these mice were scanned with power Doppler sonography at two time points over the course of treatment, and power-weighted pixel densities were assessed. The other twelve mice each underwent subcutaneous placement of a dorsal skin-fold window over the tumor site, allowing for daily angiogenesis assessment of vascular length density. All tumor specimens had correlative histologic analyses performed, including immunohistochemical stains for microvasculature. RESULTS: Sonographic measurements revealed significant longitudinal differences in tumor vascularity among the four treatment groups: control mice receiving no treatment demonstrated a doubling in intra-tumor color pixel density (P < 0.02); those receiving radiation alone increased by 68% (P < 0.04); those receiving oral therapy alone increased by 44% (P = 0.016); and those receiving combination therapy decreased by 38% (P < 0.02). Tumor vascularity independently measured in the twelve mice with the skin-fold windows revealed a similar response to each type of treatment. Post-mortem tumor histology was consistent with both sonographic and skin-fold window measurements. CONCLUSION: Power Doppler sonography was accurate and reliable in measuring tumor vascularity changes in this model. These results were independently confirmed by a quantitative method relying on direct visualization of the microvasculature. Because it is rapid and non-invasive, sonographic quantification is beneficial in assessing the anti-angiogenic effects of various treatment strategies for cancer.

Angiogenesis Inhibitors↗
PubMed2004

Quantification of tumor vascularity with contrast-enhanced sonography: correlation with magnetic resonance imaging and fluorodeoxyglucose autoradiography in an implanted tumor.

OBJECTIVE: To correlate the quantitated tumor vascularity of implanted murine tumors as depicted by contrast-enhanced sonography with estimates made with magnetic resonance imaging and with estimates of the percentage of viable (metabolically active) tumor as depicted by fluorodeoxyglucose autoradiography. METHODS: Implanted tumors in 10 mice were imaged with contrast-enhanced sonography, magnetic resonance imaging, and fluorodeoxyglucose autoradiography. Tumor vascularity was estimated with each modality and compared with the percentage of viable tumor. RESULTS: Quantitated estimates of tumor vascularity with contrast-enhanced sonography closely correlated (r = 0.95) with estimates made by magnetic resonance imaging and with the percentage of viable tumor (r = 0.93) as depicted by fluorodeoxyglucose autoradiography. CONCLUSIONS: Contrast-enhanced sonography accurately depicts tumor vascularity in these implanted tumors. Tumor vascularity correlated with the amount of metabolically active tumor.

Animals↗
PubMed2004

Sonographic depiction of microvessel perfusion: principles and potential.

OBJECTIVE: To provide an overview of the technical aspects and potential clinical applications of microvessel perfusion as depicted by microbubble-enhanced sonography. METHODS: Sonographic depiction of microvessel perfusion was obtained by microbubble-enhanced sonography. This technique was used for imaging in vivo murine tumors and was correlated with magnetic resonance and fluorodeoxyglucose autoradiography. Sonographic estimation of microvessel perfusion used parameters derived from time-activity curves. RESULTS: Preliminary data indicate that accurate and reproducible quantification of microvessel perfusion is possible with the use of microbubble-enhanced sonography. CONCLUSIONS: Microbubble-enhanced sonography can depict microvessel perfusion. This technique has several potential clinical applications, including assessment of tumor blood flow and changes that occur with treatment.

Animals↗
PubMed2003

Color Doppler sonography of uterine disorders.

Color Doppler sonography (CDS) of uterine disorders has clinical applications for the evaluation of uterine fibroids, polyps, and vascular malformations. This review describes and illustrates these applications as well as the use of 3D CDS.

Endometrial Neoplasms↗
PubMed2003

Color Doppler sonohysterography of endometrial polyps and submucosal fibroids.

OBJECTIVE: To describe the typical sonographic findings and clinical applications of color Doppler sono-hysterography and to correlate the vascularity of lesions seen on color Doppler sonohysterography to microvessel density and the presence of vessels greater than 0.5 mm. METHODS: Color Doppler sonohysterography was performed on 25 women with abnormal uterine bleeding. The vascularity (number of vessels > 0.5 mm) and their configuration seen on color Doppler sonohysterography were compared with those obtained on the excised specimen. Microvessel density and histologic features were correlated to the visualization of vessels greater than 0.5 mm and their arrangement on color Doppler sonography. RESULTS: The color Doppler sonographic findings in 18 polyps, 3 submucosal fibroids, and 1 clot showed distinct vascularity patterns. Polyps typically contained a single feeding vessel, whereas fibroids had several vessels, which arose from the inner myometrium. Lesions with higher microvessel density tended to have more vessels greater than 0.5 mm as depicted on color Doppler sonography. CONCLUSIONS: Color Doppler sonohysterography may be useful in distinguishing polyps from submucosal fibroids based on the vascularity of the lesions. The number of vessels seen on color Doppler sonography approximates microvessel density within the lesions.

Adult↗