Anne L. Hall

Subharmonic Imaging with Microbubble Contrast Agents: Initial Results

The subharmonic emission from insonified contrast microbubbles was used to create a new imaging modality called Subharmonic Imaging. The subharmonic response of contrast microbubbles to ultrasound pulses was first investigated for determining adequate acoustic transmit parameters. Subharmonic A-lines and gray scale images were then obtained using a laboratory pulse-echo system in vitro and a modified ultrasound scanner in vivo. Excellent suppression of all backscattered signals other than from contrast microbubbles was achieved for subharmonic A-lines in vitro while further optimization is required for in vivo gray scale subharmonic images.

An improved wall filter for flow imaging of low velocity flow

In medical ultrasound, flow velocity estimation for blood flow imaging (color flow) relies on first filtering out signals due to stationary scatterers so that a simple autocorrelation frequency estimator can be used to determine flow. Usually, this “wall filter” is implemented as either a conventional FIR or IIR filter. Unfortunately, in the case of very low velocity flow, these wall filters may remove signals from the moving scatterers of interest. In this work we present a novel filtering scheme that involves first shifting (via a complex multiplication) the undesired signals to zero frequency and then removing these signals by simply subtracting the average of these signals from each of them. The result is a high-pass filter which is very narrow, yet does not reduce the number of samples available to the autocorrelation velocity estimator

Contrast-enhanced ultrasound for imaging vasa vasorum: comparison with histopathology in a swine model of atherosclerosis.

AIM To evaluate the agreement between contrast-enhanced ultrasound imaging and histopathology in an animal model of atherosclerosis. METHODS AND RESULTS Atherosclerosis was studied in both femoral arteries of four Rapacz familial hypercholesterolaemia (RFH) swine. Contrast-enhanced ultrasound imaging of the eight femoral arteries was performed at baseline and at 5, 12, 26, and 43 weeks follow-up after percutaneous transluminal stimulation of atherosclerosis to assess the progression of intima-media thickness (IMT) and the density and extent of the vasa vasorum network. Contrast-enhanced ultrasound imaging allowed an early detection of atherosclerosis and showed a significant gradual progression of atherosclerosis over time. IMT increased from 0.22 +/- 0.05 mm at baseline to 0.45 +/- 0.06 mm (P < 0.001) at follow-up. The density of the vasa vasorum network increased during follow-up and was significantly higher in advanced than in early atherosclerosis. The findings with contrast-enhanced ultrasound were confirmed by histopathological specimens of the arterial wall. CONCLUSION Contrast-enhanced ultrasound is effective for in vivo detection of vasa vasorum in atherosclerotic plaques in the RFH swine model. After stimulation of atherosclerosis, contrast-enhanced ultrasound demonstrated a significantly increased IMT and significantly increased density of the vasa vasorum network in the developing atherosclerotic plaque, which was validated by histology.

In Vivo Perfusion Estimation Using Subharmonic Contrast Microbubble Signals

Objective. The purpose of this study was to quantify perfusion in vivo using contrast‐enhanced subharmonic imaging (SHI). Methods. A modified LOGIQ 9 scanner (GE Healthcare, Milwaukee, WI) operating in gray scale SHI mode was used to measure SHI time‐intensity curves in vivo. Four dogs received intravenous contrast bolus injections (dose, 0.1 mL/kg), and renal SHI was performed. After 3 contrast agent injections, a microvascular staining technique based on stable (nonradioactive) isotope‐labeled microspheres (BioPhysics Assay Laboratory Inc, Worcester, MA) was used to quantify the degree of perfusion in 8 sections of each kidney. Low perfusion states were induced by ligating surgically exposed segmental renal arteries followed by contrast agent injections and microvascular staining. Digital clips were transferred to a personal computer, and SHI time‐intensity curves were acquired in each section using Image‐Pro Plus software (Media Cybernetics, Silver Spring, MD). Subharmonic fractional blood volumes were calculated, and the perfusion was estimated from the initial slope of the fractional blood volume uptake averaged over 3 injections. Subharmonic perfusion data were compared with the gold standard (ie, the microspheres) using linear regression analysis. Results. In vivo gray scale SHI clearly showed flow and, thus, perfusion in the kidneys with almost complete suppression of tissue signals. In total, 270 SHI time‐intensity curves were acquired, which reduced to 94 perfusion estimates after averaging. Subharmonic perfusion estimates correlated significantly with microsphere results (r = 0.57; P < .0001). The best SHI perfusion estimates occurred for high perfusion states in the anterior of the kidneys (r = 0.73; P = .0001). The corresponding root mean square error was 2.4%. Conclusions. Subharmonic perfusion estimates have been obtained in vivo. The perfusion estimates were in reasonable to good agreement with a microvascular staining technique.

B-mode blood flow (B-flow) imaging

B-flow is a new technique that extends the resolution, frame rate, and dynamic range of B-mode to simultaneously image blood flow and tissue. B-flow relies on coded excitation to boost weak signals from blood scatterers and on tissue equalization to simultaneously display flowing blood and tissue without threshold decision and overlay. Various classes of codes such as Barker and Golay may be used. Clinical B-flow cineloops demonstrate 3/spl times/ resolution and frame rate improvement over color flow, which, together with over 60 dB of display dynamic range, are able to image hemodynamics and vessel walls with unprecedented clarity.

Subharmonic Contrast Microbubble Signals for Noninvasive Pressure Estimation under Static and Dynamic Flow Conditions

Our group has proposed the concept of subharmonic aided pressure estimation (SHAPE) utilizing microbubble-based ultrasound contrast agent signals for the noninvasive estimation of hydrostatic blood pressures. An experimental system for in vitro SHAPE was constructed based on two single-element transducers assembled confocally at a 60° angle to each other. Changes in the first, second and subharmonic amplitudes of five different ultrasound contrast agents were measured in vitro at static hydrostatic pressures from 0–186 mmHg, acoustic pressures from 0.35–0.60 MPa peak-to-peak and frequencies of 2.5–6.6 MHz. The most sensitive agent and optimal parameters for SHAPE were determined using linear regression analysis and implemented on a Logiq 9 scanner (GE Healthcare, Milwaukee, WI). This implementation of SHAPE was then tested under dynamic-flow conditions and compared to pressure-catheter measurements. Over the pressure range studied, the first and second harmonic amplitudes reduced approximately 2 dB for all contrast agents. Over the same pressure range, the subharmonic amplitudes decreased by 9–14 dB and excellent linear regressions were achieved with the hydrostatic pressure variations (r2 = 0.98, p < 0.001). Optimal sensitivity was achieved at a transmit frequency of 2.5 MHz and acoustic pressure of 0.35 MPa using Sonazoid (GE Healthcare, Oslo, Norway). A Logiq 9 scanner was modified to implement SHAPE on a convex transducer with a frequency range from 1.5–4.5 MHz and acoustic pressures from 0–3.34 MPa. Results matched the pressure catheter (r2 = 0.87). In conclusion, subharmonic contrast signals are a good indicator of hydrostatic pressure. Out of the five ultrasound contrast agents tested, Sonazoid was the most sensitive for subharmonic pressure estimation. Real-time SHAPE has been implemented on a commercial scanner and offers the possibility of allowing pressures in the heart and elsewhere to be obtained noninvasively.

Parametric Imaging Using Subharmonic Signals From Ultrasound Contrast Agents in Patients With Breast Lesions

Parametric maps showing perfusion of contrast media can be useful tools for characterizing lesions in breast tissue. In this study we show the feasibility of parametric subharmonic imaging (SHI), which allows imaging of a vascular marker (the ultrasound contrast agent) while providing near complete tissue suppression. Digital SHI clips of 16 breast lesions from 14 women were acquired. Patients were scanned using a modified LOGIQ 9 scanner (GE Healthcare, Waukesha, WI) transmitting/receiving at 4.4/2.2 MHz. Using motion‐compensated cumulative maximum intensity (CMI) sequences, parametric maps were generated for each lesion showing the time to peak (TTP), estimated perfusion (EP), and area under the time‐intensity curve (AUC). Findings were grouped and compared according to biopsy results as benign lesions (n = 12, including 5 fibroadenomas and 3 cysts) and carcinomas (n = 4). For each lesion CMI, TTP, EP, and AUC parametric images were generated. No significant variations were detected with CMI (P = .80), TTP (P = .35), or AUC (P = .65). A statistically significant variation was detected for the average pixel EP (P = .002). Especially, differences were seen between carcinoma and benign lesions (mean ± SD, 0.10 ± 0.03 versus 0.05 ± 0.02 intensity units [IU]/s; P = .0014) and between carcinoma and fibroadenoma (0.10 ± 0.03 versus 0.04 ± 0.01 IU/s; P = .0044), whereas differences between carcinomas and cysts were found to be nonsignificant. In conclusion, a parametric imaging method for characterization of breast lesions using the high contrast to tissue signal provided by SHI has been developed. While the preliminary sample size was limited, results show potential for breast lesion characterization based on perfusion flow parameters.

Measurement of Volumetric Flow

Objective. The purpose of this study was to evaluate a 3‐dimensional (3D) sonographic method for the measurement of volumetric flow under conditions of known flow rates and Doppler angles. Methods. A GE/Kretz Voluson 730 system (GE Healthcare, Milwaukee, WI) and RAB2‐5 probe were used to acquire 3D Doppler measurements in a custom flow phantom. Blood‐mimicking fluid circulated by a computer‐controlled pump provided a range of flow velocities (2–15 mL/s). A 6‐axis positioning system maneuvered the ultrasound probe through a range of angles (40°–70° and 110°–140°) with respect to the tube (orthogonal to the tube being 90°). Volume data sets were obtained spanning 29° lateral and 20° elevational angles encompassing the flow tube in a scanning time of less than 10 seconds. Power Doppler data were used to correct for partial volume effects. Results. Using a single angle (110°) with respect to the flow tube, measured and actual volume flow rates were within the 95% confidence interval over the full range of flow rates. At flow rates of 5 and 10 mL/s, the measured volume flow rates were all within ±15% of actual values for the range of angles tested and also stayed within the 95% confidence interval. Conclusions. Direct comparisons of volume flow rates estimated with 3D sonography and known flow rates showed that the method has good accuracy. Subsequent comparisons under pulsatile and in vivo conditions will be needed to verify this performance for clinical applications.

Static and Dynamic Cumulative Maximum Intensity Display Mode for Subharmonic Breast Imaging A Comparative Study With Mammographic and Conventional Ultrasound Techniques

Objective. The purpose of this study was to test the efficacy of static and dynamic cumulative maximum intensity (CMI) subharmonic imaging (SHI) in breast ultrasound studies. Methods. Contrast‐enhanced SHI was performed in 14 women using a modified LOGIQ 9 scanner (GE Healthcare, Milwaukee, WI) transmitting/receiving at 4.4/2.2 MHz. Following mammography, baseline scans of gray scale ultrasound and power Doppler imaging (PDI) were performed. Contrast‐enhanced PDI and gray scale SHI were performed after contrast agent administration. Static CMI‐SHI is a composite image summarizing blood flow over multiple frames using the maximum intensity projection technique. The dynamic CMI‐SHI mode depicts the gradual inflow pattern of the contrast agent in blood vessels. Both CMI‐SHI modes were set up using a new automated sum‐absolute‐difference–based block‐matching algorithm to reduce noise and blurring and compensate for motion artifacts. Evaluation of the imaging modes for detecting breast cancer was done by an experienced radiologist, blinded to histopathologic findings. Sensitivity, specificity, and receiver operating characteristic (ROC) analyses were computed and compared for all ultrasound imaging modes and mammography. Results Of the 16 lesions, 4 were malignant. The area under the ROC curve (Az) for the diagnosis of breast cancer was 0.64 for gray scale and PDI, 0.67 for contrast‐enhanced PDI, 0.76 for mammography, 0.78 for SHI, and 0.75 for static CMI‐SHI. For the dynamic CMI‐SHI mode, the Az increased to 0.90, and this was significantly better than mammography (P = .03). Conclusions. The new dynamic CMI‐SHI mode produced the highest Az for the diagnosis of breast cancer compared to conventional techniques and thus appears to improve diagnosis of breast cancer relative to conventional techniques, albeit based on a limited patient population.

Ultrasound image display by combining enhanced flow imaging in B-mode and color flow mode

An ultrasound system (1) acquires data using a gray scale mode of operation and a color flow mode of operation. A transducer (10) generates receive signals in response to echo ultrasound waves received from a subject (S) being studied. A gray scale receive channel (9G) generates gray scale data representing movement of portions of the subject, in particular that of blood flow or contrast agents in blood or tissue. A color flow receive channel (9C) generates color flow data (e.g., either power data or velocity data) also representing movement of portions of the subject. A processor (30) combines the gray scale flow data with the color flow data and displays the result on a display monitor (19) such that moving portions of the subject are displayed with a colored gray scale image.