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Biomedical subjects

Robert F Mattrey

Publications and source records attributed to Robert F Mattrey.

At least 19 recordsLinked to original sources
PubMed2006

Time course and role of morphine dose and concentration in intrathecal granuloma formation in dogs: a combined magnetic resonance imaging and histopathology investigation.

BACKGROUND: Intrathecal morphine infusion leads to intrathecal granulomas. In dogs, the authors examined time course of granuloma formation and the role of concentration in granuloma development. METHODS: Dogs were prepared with lumbar intrathecal catheters and vest-mounted pumps. To define the time course of granuloma formation, serial magnetic resonance imaging was performed in animals receiving 10 or 31 days of morphine infusion (12.5 mg/ml at 40 microl/h). At these times, morphine was removed from the infusate, and further magnetic resonance images were acquired over 14-35 additional days. To assess dose versus concentration, dogs received 28-day infusions of vehicle, 12 mg morphine/day as 12.5 mg/ml at 40 microl/h, or 1.5 mg/ml at 334 microl/h (12 mg/day) for 28 days. Additional dogs received 3 mg/day as 12.5 mg/ml at 10 mul/h. RESULTS: Serial magnetic resonance images in dogs receiving morphine (12.5 mg/ml at 40 microl/h) revealed pericatheter-enhancing tissues as early as 3 days with a prominent signal by 10 days. Removal of morphine reduced the mass volume within 7 days. At a fixed infusion rate, the incidence of granuloma formation with the continuous intrathecal infusion of morphine ranged from 0 in vehicle-treated dogs to 100% in dogs treated with 12.5 mg/ml at 40 microl/h (12 mg/day). Infusion of 12 mg/day at 1.5 mg/ml (334 microl/h) resulted in granuloma in one of four animals. The authors found that infusion of morphine in different concentrations at a fixed rate resulted in a dose-dependent increase in concentration, with the granuloma-producing, dose-yielding lumbar cerebrospinal fluid morphine concentrations around 40 microg/ml. CONCLUSIONS: Serial magnetic resonance imaging showed a rapid formation and regression of the masses initiated by intrathecal morphine infusion. These masses are dependent on local concentration.

Animals↗
PubMed2006

Accuracy of ultrasonography and magnetic resonance imaging in the diagnosis of placenta accreta.

BACKGROUND: The incidence of placenta accreta has increased dramatically over the last three decades, in concert with the increase in the cesarean delivery rate. Optimal management requires accurate prenatal diagnosis. The purpose of this study was to determine the precision and reliability of ultrasonography and magnetic resonance imaging (MRI) in diagnosing placenta accreta. METHODS: A historical cohort study was performed with information gathered from our obstetric, radiologic, and pathology databases. Records from January 2000 to June 2005 were reviewed to identify patients with a diagnosis of placenta previa, low-lying placenta with a prior cesarean delivery, or history of a myomectomy to determine the accuracy of pelvic ultrasonography in the diagnosis of placenta accreta. The records of those considered to be suspicious for placenta accreta and subsequently referred for additional confirmation by MRI were also analyzed. The sonographic and MRI diagnoses were compared with the final pathologic or operative findings or with both. RESULTS: Of the 453 women with placenta previa, previous cesarean delivery and low-lying anterior placenta, or previous myomectomy, 39 had placenta accreta confirmed by pathological examination. Ultrasonography accurately predicted placenta accreta in 30 of 39 of women and correctly ruled out placenta accreta in 398 of 414 without placenta accreta (sensitivity 0.77, specificity 0.96). Forty-two women underwent MRI evaluation because of findings suspicious or inconclusive of placenta accreta by ultrasonography. Magnetic resonance imaging accurately predicted placenta accreta in 23 of 26 cases with placenta accreta and correctly ruled out placenta accreta in 14 of 14 (sensitivity 0.88, specificity 1.0). CONCLUSION: A two-stage protocol for evaluating women at high risk for placenta accreta, which uses ultrasonography first, and then MRI for cases with inconclusive ultrasound features, will optimize diagnostic accuracy.

Adult↗
PubMed2006

Angiogenesis: noninvasive quantitative assessment with contrast-enhanced functional US in murine model.

PURPOSE: To evaluate quantitative functional ultrasonography (US) in a murine gel model by using microbubble destruction kinetics to determine whether parametric indices provided with US could help assess angiogenesis. MATERIALS AND METHODS: Institutional Animal Subjects Committee approved experiments and procedures. In 36 normal mice, two 0.4-mL gel implants were placed subcutaneously on either side of spine. One implant contained 0.5, 1.0, or 1.5 microg human basic fibroblast growth factor (bFGF) per milliliter of gel. Functional US quantitative analysis of angiogenesis with microbubble contrast agent was performed on days 3, 6, 9, and 12; histologic data were collected. Time-intensity curve of implant was fitted to mathematic decay model to calculate fractional blood volume and fraction of blood replaced per unit of time. Microvascular density (MVD) and percentage of microvascular area (MVA) were measured after anti-CD31 staining. Spearman rank order correlation was used in analyses. RESULTS: bFGF-containing implants induced MVD of eight, 35, 42, and 42 vessels per square millimeter on days 3, 6, 9, and 12, respectively; in controls, MVD was four vessels/mm2 (P<.05 on days 6, 9, and 12). bFGF-containing implants induced percentage MVA of 2%, 5%, 20%, and 27%, respectively; in controls, it was 0.5% (P<.05). Maximum enhancement was significantly increased in bFGF implants (23.3 gray level+/-14.1 [standard deviation]) compared with controls (11.0+/-5.5, P<.001). Implants containing bFGF showed poor correlations between fractional blood volume and MVD (r2=0.42) or percentage MVA (r2=0.51) at US. There was no correlation between microbubble velocity and MVD (r2<0.05) or percentage MVA (r2<0.13). CONCLUSION: Functional US perfusion parameters do not correlate with current histologic indices for quantifying angiogenesis. MVD, as a histologic quantitative measurement of angiogenesis, may not be an appropriate standard for contrast-enhanced imaging that relies on perfused neovessels.

Animals↗
PubMed2005

Cy5.5-DTPA-galactosyl-dextran: a fluorescent probe for in vivo measurement of receptor biochemistry.

The high sensitivity of fluorescent reporters offers an opportunity to analytically probe the biochemistry of in vivo receptor systems with low target tissue concentration. We investigated the ability of an optical imaging system to acquire adequate signal for in vivo measurement of receptor biochemistry. The imaging system consisted of a small animal optical imager operating in the time domain (TD) and a fluorescent-labeled diagnostic probe of known receptor-binding properties. Optical imaging of mice (n = 4) using the targeted probe, Cy5.5-DTPA-galactosyl-dextran (2.2 Cy5.5, 4 DTPA, 68 galactose units per dextran, 124 kDa, 24 nmol/kg), demonstrated blood clearance and hepatic uptake. The mean and standard deviation for the time to reach 90% of the peak liver intensity were 15.4 +/- 1.6 min. Typical fluorescent intensities within a 10-pixel region-of-interest from a 30-s image acquired 30 min postinjection were in excess of 2.5 million counts. The nontargeted agent (Cy5.5-DTPA-dextran) did not demonstrate (n = 4) hepatic uptake. This uptake pattern was duplicated by nuclear imaging of rabbits using (99m)Tc-labeled Cy5.5-DTPA-galactosyl-dextran and Cy5.5-DTPA-dextran. This study demonstrated the feasibility of optically labeling a receptor-binding diagnostic probe and imaging in the TD with sufficient sensitivity and temporal resolution for pharmacokinetic analysis.

Animals↗
PubMed2005

Ultrasound of the liver.

This article summarizes the recent advances in ultrasound imaging of the liver, especially contrast-enhanced imaging. Contrast-enhanced ultrasound has dramatically changed the role of ultrasound in liver tumor characterization, detection, and other applications. Available ultrasound contrast agents, agents under development, contrast-specific imaging techniques, and its applications in liver imaging are discussed.

Contrast Media↗
PubMed2005

Transcranial ultrasound angiography (T USA): a new approach for contrast specific imaging of intracranial arteries.

The goal was to develop an ultrasound contrast agent-specific imaging mode that offers an angiography-like view of the intracranial arteries and enables lower mechanical index MI settings compared to conventional transcranial duplex sonography. We studied 12 patients with transcranial ultrasound angiography (t USA) via the temporal bone window after an IV bolus injection of a perfluorocarbon-based microbubble contrast agent (Imagent). The aim was to display the intracranial vessel segments of the middle cerebral artery (M1, M2 and M3), the anterior cerebral artery (A1 and A2), the posterior cerebral artery (P1, P2 and P3) and the internal carotid artery (C1/2 and C3/4). t USA is a B-mode phase inversion imaging technique that uses wideband harmonic signals for image generation. We demonstrate, in this report, that t USA provides detailed anatomical display at native B-mode spatial resolution with fewer artifacts, yielding improved delineation of intracranial vessels that are in the 1- to 2-mm range.

Adolescent↗
PubMed2005

MRI of the female pelvis using vaginal gel.

OBJECTIVE: Vaginal distention with aqueous gel optimizes MRI evaluation of the vaginal walls and outer contours of the cervix. The objective of this pictorial essay is to illustrate the use of vaginal gel for MRI of the female pelvis. CONCLUSION: Distention of the vagina with gel is an inexpensive, well-tolerated procedure that may improve MRI evaluation of a variety of gynecologic conditions.

Adult↗
PubMed2004

Gadolinium-DTPA-dextran: a macromolecular MR blood pool contrast agent.

RATIONALE AND OBJECTIVES: Magnetic resonance (MR) imaging blood pool agents offer numerous advantages for vascular and tumor imaging. The purpose of this study was to test gadolinium-diethylenetriaminepentaacetate-dextran ([Gd]DTPA-dextran) as a new water soluble macromolecular blood pool agent for MR imaging. MATERIALS AND METHODS: [Gd]DTPA-dextran (187 gadolinium atoms per dextran, molecular weight 165 kD, diameter 17.6 nm) was synthesized. Fifteen anesthetized New Zealand White rabbits with thigh VX2 tumors were scanned in a knee coil at 1.5T. Coronal 3D MR angiographic sequences were obtained before and at several time points up to 72 hours after the intravenous bolus injection of [Gd]DTPA-dextran providing gadolinium at either 0.05 (n = 4) or 0.1 mmol/kg (n = 8) or [Gd]DTPA-bismethylamide (BMA) providing gadolinium at 0.1 mmol/kg (n = 3). Time enhancement curves for aorta, cava, and tumor rim were compared by univariate General Linear Model. RESULTS: Contrast enhancement of cava and aorta relative to a water phantom were significantly greater at all time points after either dose of [Gd]DTPA-dextran than after [Gd]DTPA-BMA (P < 0.01). Tumor rim enhancement was less intense for either dose of [Gd]DTPA-dextran at peak than for [Gd]DTPA-BMA (P < 0.05). Tumor rim enhancement with both doses of [Gd]DTPA-dextran became equivalent to that of [Gd]DTPA-BMA at one hour and was greater at 24 hours (P < 0.05). CONCLUSION: [Gd]DTPA-dextran is a new macromolecular MR contrast agent that can be synthesized to carry a high density of gadolinium atoms without intra-molecular cross-linking. It provides significantly greater vascular residence time than a conventional gadolinium chelate and shows promise for MR blood pool imaging.

Animals↗
PubMed2004

Angiogenesis model for ultrasound contrast research: exploratory study.

RATIONALE AND OBJECTIVES: To optimize an angiogenesis model for imaging research that is stable and can be imaged several times over the angiogenic time course. MATERIALS AND METHODS: Mice and rats received two injections of 0.4 mL of extract of basement membrane matrix (Matrigel; Becton Dickinson Labware, Bedford, MA) in the subcutaneous spaces on either side of the spine. One of the two Matrigel plugs in each animal had either 0.1 microg/mL of basic fibroblast growth factor (bFGF) (11 mice), 1.0 microg/mL of bFGF (12 mice, 5 rats), or 1.0 microg/mL of bFGF and 60 U/mL of heparin (11 mice). Three to 12 days after implantation, animals were imaged before and after the administration of up to four injections of 0.1 mL AF0150. Phase inversion imaging was used on a Siemens Elegra (Siemens ultrasound, Issaquah, WA) equipped with a 13 MHz VFX transducer. Three observers subjectively assessed the pattern of enhancement using a four-point scale. The Matrigel plugs were then removed and two observers graded the angiogenic response on a four-point scale. Ten Matrigel plugs, five with 1.0 microg/mL bFGF and five without, were evaluated histologically following immunohistochemical staining with anti-CD31. RESULTS: The angiogenic response was greater in Matrigel plugs with 1.0 than with 0.1 microg/mL of bFGF. Heparin did not increase the angiogenic response. Vessels were predominantly at the periphery of the plugs with variable central penetration. Plugs appeared anechoic and homogeneous on ultrasound. Contrast enhancement within the plug occurred in 44% of mice with an angiogenic response at or after day 6 and the enhancement increased with the angiogenic response. In the others, peripheral enhancement could not be distinguished from the enhancement of surrounding tissues that were also hyperemic. The thicker rat skin interfered with plug assessment. CONCLUSION: A stable angiogenesis model without the complexity of tumors is described. This model offers the opportunity to image the development and/or inhibition of angiogenesis. Neovasculature in Matrigel was detectable using ultrasound contrast. Quantitative studies correlating the degree of enhancement to microvascular density will be determined in subsequent studies.

Animals↗
PubMed2004

Model to quantify lymph node enhancement on indirect sonographic lymphography.

OBJECTIVE: Our goal was to develop a reliable technique that has minimal operator dependence for quantifying lymph node enhancement to test and optimize new sonography contrast formulations. MATERIALS AND METHODS: Twenty healthy rabbits were studied using five agents, labeled A-G. Agents D and E were the same agent and agents F and G were Imagent, studied blindly to test reproducibility. One milliliter of contrast agent was injected into each hind footpad. A 13-MHz transducer was fixed over the popliteal node, which was imaged at a 4.8-MHz central transmit frequency using phase-inversion technology at 100% power and one frame per second. Immediately after each injection, the footpad was massaged 12 times for 30 sec each time and then imaged after each massage to assess the number of times the node could be refilled from each injection. Lymph node video intensity was measured, and the degree of enhancement was evaluated using analysis of variance with the massage number and the agent used as independent variables. RESULTS: Lymph node enhancement was observed after the first massage with all agents. Degree of enhancement was least with agents A and B, intermediate with agents D and F, and greatest with agent C. Agent A was effective after the first two massages, agent B after the first four, agent C after all 12, agent D after the first eight, and agent F after the first nine. Performance of agents D and F was similar to that of their duplicates, E and G. CONCLUSION: We established a reproducible technique to quantify lymph node enhancement that can distinguish between different agents. The differences in performance suggest that it is possible to optimize agent formulation for indirect sonographic lymphography.

Analysis of Variance↗
PubMed2004

Noninvasive estimation of the pressure gradient across stenoses using sonographic contrast: in vitro validation.

OBJECTIVE: Because velocity measurements to estimate the degree of arterial stenosis are susceptible to local and systemic factors, we aimed to investigate the feasibility of estimating the pressure gradient across a stenosis noninvasively by using sonographic contrast. METHODS: Using a gravity-fed flow system, a 1:4000 dilution of a contrast agent in water was circulated through silicone tubes that had either focal or long-segment stenoses of varying severity in a water bath. We measured the cross-sectional areas of the normal and stenotic regions with B-mode sonography and the flow velocity with spectral Doppler sonography and calculated the pressure gradients across the stenoses using the empirically derived Young mathematical model and the simplified Bernoulli equation. Estimated gradients were compared with those measured manometerically. RESULTS: Both methods yielded estimates of pressure gradients that correlated with measured gradients (r > 0.988). In focal and long-segment stenoses, the Young model yielded gradients that agreed more closely with manometerically measured values than the Bernoulli equation (+/- 8% versus -24%-57%). Both methods were highly dependent on the ability to measure the luminal cross-sectional area. The presence of sonographic contrast in the vascular lumen highlighted the inner wall, allowing the accurate measurement of the luminal area to +/- 3.0%. CONCLUSIONS: The pressure gradient can be estimated across stenoses noninvasively. The Young model was more accurate than the simplified Bernoulli equation in this model using steady flow. Estimated gradients are highly dependent on the definition of the vascular lumen, a process aided by the use of sonographic contrast.

Carotid Stenosis↗
PubMed2003

Carotid arteries: contrast-enhanced US angiography--preliminary clinical experience.

B-mode ultrasonographic (US) angiography enhanced with a microbubble-based US contrast agent (FS069) was evaluated in human subjects with carotid artery disease. Results at contrast material-enhanced US angiography and duplex US were compared with those at conventional angiography. Both US angiography and duplex US accurately depicted stenoses of 70% or more compared with those depicted at conventional angiography. The percentage diameter stenosis of the internal carotid artery measured at US angiography strongly correlated with that measured at conventional angiography (r = 0.988). The percentage area stenosis measured at US angiography strongly correlated with ex vivo measurements of the resected carotid plaque at magnetic resonance imaging (r = 0.979). US angiography depicted unsuspected wall irregularities, ulceration, and dissection.

Aged↗
PubMed2003

Validation of ultrasound contrast destruction imaging for flow quantification.

Our purpose was to validate in vitro a kinetic flow model based on microbubble signal decay curve. Using a 3.5 MHz transducer and phase-inversion (1.8 MHz central transmit frequency), a renal dialysis cartridge oriented vertically was imaged in the transverse plane as 1:1000 dilution of AF0150 was infused at 50, 100, 200, 300 and 400 mL/min. Ten gray-scale images were acquired at each infusion rate using 2.5, 5 and 10 frames/s at 100%, 40%, 15% or 1% of maximum transmit power. Video-intensity measured on each 10 images was fit to a kinetic model using Sigma Plot that yielded microbubble concentration, velocity and destruction per frame. These were correlated with the experimental conditions. At 100% power, video-intensity on the first frame (microbubble concentration at equilibrium) was similar for all flow and frame rates. The model fit the experimental data for all flows at 10 frames/s and for flows lower than 400 and 100 mL/min at 5 frames/s and 2.5 frames/s, respectively. The calculated flow was similar to the experimental flow rates, regardless of technique (r(2) = 0.98). Microbubble fraction destroyed per frame was similar for all flow and frame rates and increased linearly with transmit power (r(2) > 0.98). These results suggest that using appropriate power and frame rate for a given flow rate, estimates of fractional blood volume, flow and destruction fraction can be calculated from the decay curve using 10 frames that can be acquired in 1 to 4 s.

Contrast Media↗
PubMed2002

A molecular CT blood pool contrast agent.

RATIONALE AND OBJECTIVES: A molecular-based computed tomographic (CT) contrast agent with prolonged vascular residence time is needed for vascular and tumor imaging. No particulate agents have reached clinical practice due to nonspecific macrophage activation. The authors' objective was to synthesize a water-soluble macromolecular agent. MATERIALS AND METHODS: Dysprosium-DTPA-dextran was synthesized through activation of the hydroxyl units of dextran PM40 with allylbromine and subsequent reaction with amino ethanethiol to produce amino-terminated leashes. These leashes were then coupled to DTPA by means of the mixed anhydride method. Complexation of dysprosium by DTPA-dextran was achieved in an acidic solution of 0.2 M dysprosium chloride. One rabbit with a VX2 tumor was imaged with [Dy]DTPA-dextran (0.5 mL, 3.1 g, 1.15 mmol of dysprosium per kilogram). Transaxial scans were acquired through the liver and tumor for 45 minutes. A second healthy rabbit was imaged with Optiray-320 (6.0 mL, 5.0 mmol of iodine per kilogram) at 1-minute intervals for 10 minutes and again at 20 minutes. RESULTS: Each dextran PM40 molecule (diameter, 8.8 nm) contained 95 [Dy]DTPA groups, increasing its average molecular weight from 40,500 to 101,537 g/mol. The baseline-corrected inferior vena cava (IVC) enhancement for [Dy]DTPA-dextran decreased, with an 8-minute half-time during the first 15 minutes followed by a nearly zero slope for the rest of the observation period. The IVC remained brighter than liver throughout the observation period. The solid portion of the tumor was enhanced by 5-10 CT numbers, rendering areas of necrosis more apparent. The baseline-corrected IVC curve for Optiray-320 also demonstrated two phases, with half-times of 2.5 and 45 minutes. The IVC became less dense than liver within 5-8 minutes. CONCLUSION: [Dy]DTPA-dextran is water soluble and can be synthesized without intermolecular cross-linking to carry a high load of dysprosium. It provides blood pool enhancement characteristics with a long intravascular dwell time.

Animals↗
PubMed2002

Multimodality diagnosis of liver tumors: feature analysis with CT, liver-specific and contrast-enhanced MR, and a computer model.

RATIONALE AND OBJECTIVES: The purpose of this study was to measure and to clarify the diagnostic contributions of image-based features in differentiating benign from malignant and hepatocyte-containing from non-hepatocyte-containing liver lesions. MATERIALS AND METHODS: Six experienced abdominal radiologists each read images from 146 cases (including a contrast material-enhanced computed tomographic [CT] scan and contrast-enhanced and unenhanced magnetic resonance [MR] images) following a checklist-questionnaire requiring them to rate quantitatively each of as many as 131 image features and then reported on each of the two differentiations. The diagnostic value of each feature was assessed, and linear discriminant analysis was used to develop statistical prediction rules (SPRs) for merging feature data into computerized "second opinions." For the two differentiations, accuracy (area under the receiver operating characteristic curve [Az]) was then determined for the radiologists' readings by themselves and for each of three SPRs. RESULTS: Thirty-seven candidate features had diagnostic value for each of the two differentiations (a slightly different feature set for each). Radiologists' performance at both differentiations was excellent (Az = 0.929 [benign vs malignant] and 0.926 [hepatocyte-containing vs non-hepatocyte-containing]). Performance of the SPR that operated on the features from all modalities together was better than that of radiologists (Az = 0.936 [benign vs malignant] and 0.951 [hepatocyte-containing vs non-hepatocyte-containing]), but this difference was of marginal statistical significance (P = .11). Contrast-enhanced MR imaging and contrast-enhanced CT each made significant adjunctive contributions to accuracy compared with unenhanced MR imaging alone. CONCLUSION: Many CT- and MR imaging-based features have diagnostic value in differentiating benign from malignant and hepatocyte-containing from non-hepatocyte-containing liver lesions. Radiologists could also benefit from the fully informed SPR's "second opinions."

Adult↗