Color Flow Ultrasound Spatial Sampling Beam Density for Partial Volume-Corrected Three-Dimensional Volume Flow (3DVF): Theory, Simulation, and Experiment.

OBJECTIVE: The purpose of this study was to quantify the accuracy of partial volume-corrected three-dimensional volume flow (3DVF) measurements as a function of spatial sampling beam density using carefully-designed parametric analyses in order to inform the target applications of 3DVF. METHODS: Experimental investigations employed a mechanically-swept curvilinear ultrasound array to acquire 3D color flow (6.3 MHz) images in flow phantoms consisting of four lumen diameters (6.35, 4.88, 3.18 and 1.65 mm) with volume flow rates of 440, 260, 110 and 30 mL/min, respectively. Partial volume-corrected three-dimensional volume flow (3DVF) measurements, based on the Gaussian surface integration principle, were computed at five regions of interest positioned between depths of 2 and 6 cm in 1 cm increments. At each depth, the color flow beam point spread function (PSF) was also determined, using in-phase/quadrature data, such that 3DVF bias could then be related to spatial sampling beam density. Corresponding simulations were performed for a laminar parabolic flow profile that was sampled using the experimentally-measured PSFs. Volume flow was computed for all combinations of lumen diameters and the PSFs at each depth. RESULTS: Accurate 3DVF measurements, i.e., bias less than ±20%, were achieved for spatial sampling beam densities where at least 6 elevational color flow beams could be positioned across the lumen. In these cases, greater than 8 lateral color flow beams were present. PSF measurements showed an average lateral-to-elevational beam width asymmetry of 1:2. Volume flow measurement bias increased as the color flow beam spatial sampling density within the lumen decreased. CONCLUSION: Applications of 3DVF, particularly those in the clinical domain, should focus on areas where a spatial sampling density of 6 × 6 (lateral x elevational) beams can be realized in order to minimize measurement bias. Matrix-based ultrasound arrays that possess symmetric PSFs may be advantageous to achieve adequate beam densities in smaller vessels.

Volumetric blood flow in transjugular intrahepatic portosystemic shunt revision using 3-dimensional Doppler sonography.

OBJECTIVES: Three-dimensional (3D)/4-dimensional (4D) sonographic measurement of blood volume flow in transjugular intrahepatic porto systemic shunt revision with the intention of objective assessment of shunt patency. METHODS: A total of 17 patients were recruited (12 male and 5 female; mean age, 55 years; range, 30-69 years). An ultrasound system equipped with a 2.0-5.0-MHz probe was used to acquire multivolume 3D/4D color Doppler data sets to assess prerevision and postrevision shunt volume flow. Volume flow was computed offline based on the principle of surface integration of Doppler-measured velocity vectors in a lateral-elevational c-surface positioned at the color flow focal depth (range, 8.0-11.5 cm). Volume flow was compared to routine measurements of the prerevision and postrevision portosystemic pressure gradient. Prerevision volume flow was compared with the outcome to determine whether a flow threshold for revision could be defined. RESULTS: Linear regression of data from revised transjugular intrahepatic portosystemic shunt cases showed an inverse correlation between the mean-normalized change in prerevision and postrevision shunt volume flow and the mean-normalized change in the prerevision and postrevision portosystemic pressure gradient (r(2) = 0.51; P = .020). Increased shunt blood flow corresponded to a decreased pressure gradient. Comparison of prerevision flows showed preliminary threshold development at 1534 mL/min, below which a shunt revision may be recommended (P = .21; area under the receiver operating characteristic curve = 0.78). CONCLUSIONS: Shunt volume flow measurement with 3D/4D Doppler sonography provides a potential alternative to standard pulsed wave Doppler metrics as an indicator of shunt function and predictor of revision.

Three-dimensional sonographic measurement of blood volume flow in the umbilical cord.

OBJECTIVES: Three-dimensional (3D) umbilical cord blood volume flow measurement with the intention of providing a straightforward, consistent, and accurate method that overcomes the limitations associated with traditional pulsed wave Doppler flow measurement and provides a means by which to recognize and manage at-risk pregnancies. METHODS: The first study involved 3D sonographic volume flow measurements in 7 healthy ewes whose pregnancies ranged from 18 to 19 weeks' gestation (7 singletons). Sonographic umbilical arterial and venous flow measurements from each fetus were compared to the corresponding average measured arterial/venous flow to assess the feasibility of measurement in a static vessel. A second complementary study involved 3D sonographic volume flow measurements in 7 healthy women whose pregnancies ranged from 17.9 to 36.3 weeks' gestation (6 singletons and 1 twin). Umbilical venous flow measurements were compared to similar flow measurements reported in the literature. Pregnancy outcomes were abstracted from the medical records of the recruited patients. RESULTS: In the fetal sheep model, arterial/venous flow comparisons yielded errors of 10% or less for 8 of the 9 measurements. In the clinical study, venous flow measurements showed agreement with the literature over a range of gestational ages. Two of the 7 patients in the clinical study had lower flow than anticipated for gestational age; one had a subsequent diagnosis of intrauterine growth restriction, and the other had preeclampsia. CONCLUSIONS: Accurate measurement of umbilical blood volume flow can be performed with relative ease in both the sheep model and in humans using the proposed 3D sonographic flow measurement technique. Results encourage further development of the method as a means for diagnosis and identification of at-risk pregnancies.

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 degree 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 (r = 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.

Real-time co-registration using novel ultrasound technology: ex vivo validation and in vivo applications.

OBJECTIVE: The study objective was to evaluate whether a novel global position system (GPS)-like position-sensing technology will enable accurate co-registration of images between imaging modalities. Co-registration of images obtained by different imaging modalities will allow for comparison and fusion between imaging modalities, and therefore has significant clinical and research implications. We compared ultrasound (US) and magnetic resonance imaging (MRI) scans of carotid endarterectomy (CEA) specimens using a novel position-sensing technology that uses an electromagnetic (EM) transmitter and sensors mounted on a US transducer. We then evaluated in vivo US-US and US-MRI co-registration. METHODS: Thirteen CEA specimens underwent 3.0 Tesla MRI, after which images were uploaded to a LOGIQ E9 3D (GE Healthcare, Wauwatosa, WI) US system and registered by identifying two to three common points. A similar method was used to evaluate US-MRI co-registration in patients with carotid atherosclerosis. For carotid intima-media thickness (C-IMT) measurements, 10 volunteers underwent bilateral carotid US scans co-registered to three-dimensional US maps created on the initial visit, with a repeat scan 2 days later. RESULTS: For the CEA specimens, there was a mean of 20 (standard error [SE] 2.0) frames per MRI slice. The mean frame difference, over 33 registration markers, between MRI and US scans for readers 1 and 2 was -2.82 ± 19.32 and 2.09 ± 14.68 (mean ± 95% CI) frames, respectively. The US-MRI intraclass correlation coefficients (ICCs) for the first and second readers were 0.995 and 0.997, respectively. For patients with carotid atherosclerosis, the mean US frames per MRI slice (9 [SE 2.3]) was within range of that observed with CEA specimens. Inter-visit, intra-reader, and inter-reader reproducibility of C-IMT measurements were consistently high (side-averaged ICC >0.9). CONCLUSION: Accurate co-registration between US and other modalities is feasible with a GPS-like technology, which has significant clinical and research applicability.

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.

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 (A(z)) 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 A(z) increased to 0.90, and this was significantly better than mammography (P = .03). CONCLUSIONS: The new dynamic CMI-SHI mode produced the highest A(z) 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.

Mean volume flow estimation in pulsatile flow conditions.

To verify a previously reported three-dimensional (3D) ultrasound method for the measurement of time-average volumetric blood flow, experiments were performed under pulsatile flow conditions, including in vivo investigations, and results were compared with accepted, but invasive, "gold standard" techniques. Results showed that volume averaging results in the correct time-average volume flow without the need for cardiac gating. Unlike other currently employed methods, this method is independent of Doppler angle, flow profile and vessel geometry. A GE Logiq 9 ultrasound system (GE Medical Systems, Milwaukee, WI, USA) and a four-dimensional (4D) 10L and 4D 16L probe were used to acquire 3D Doppler measurements in the femoral and carotid arteries of four canines. Two invasive blood flow meters were used (electromagnetic for one canine and ultrasonic for three canines) as the gold standard techniques. Transcutaneous color flow measurements were taken to obtain 3D volume data sets encompassing the vessel. Constant depth planes were used to integrate color flow pixels encompassing the entire vessel cross-section. Power Doppler data were used to correct for partial volume effects. An artificial stenosis was induced to vary the ambient volume flow. Unrestricted, bidirectional flow was measured as high as 400 mL min(-1). Several flow restrictions were imposed that decreased the measured volumetric flow rate to as low as 30 mL min(-1). All flow rate estimates (n=38) were plotted against results obtained via the gold standards. A general line fit resulted in y = 0.926 x - 0.87 (r(2) = 0.95), which corresponds to a 0.6% flow offset relative to the average flow rate of 142 mL min(-1), as well as a 7.4% error in the linearity of our estimate. A secondary curve fit was performed that required the slope to be 1 and the intercept to be 0, which yielded an r(2)-value of 0.93. The percent-error distribution was computed and fitted to a Gaussian function, which yielded mu=-7.04% and sigma=9.52%. Theoretical studies were conducted to estimate the expected error in our volume flow measurements as a function of number of samples (N) used for averaging pulsatile waveforms. Experiments showed the same 1/N dependence as theory. Direct comparisons of volume flow rate estimates using volumetric color Doppler and independent standards showed that our method has good accuracy under in vivo pulsatile blood flow conditions.

Characterization of cysts using differential correlation coefficient values from two dimensional breast elastography: preliminary study.

Although simple cysts are easily identified using sonography, description and management of nonsimple cysts remains uncertain. This study evaluated whether the correlation coefficient differences between breast tissue and lesions, obtained from 2D breast elastography, could potentially distinguish nonsimple cysts from cancers and fibroadenomas. We hypothesized that correlation coefficients in cysts would be dramatically lower than surrounding tissue because noise, imaging artifacts, and particulate matter move randomly and decorrelate quickly under compression, compared with solid tissue. For this preliminary study, 18 breast lesions (7 nonsimple cysts, 4 cancers, and 7 fibroadenomas) underwent imaging with 2D elastography at 7.5 MHz through a TPX (a polymethyl pentene copolymer) 2.5 mm mammographic paddle. Breasts were compressed similar to mammographic positioning and then further compressed for elastography by 1 to 7%. Images were correlated using 2D phase-sensitive speckle tracking algorithms and displacement estimates were accumulated. Correlation coefficient means and standard deviations were measured in the lesion and adjacent tissue, and the differential correlation coefficient (DCC) was introduced as the difference between these values normalized to the correlation coefficient of adjacent tissue. Mean DCC values in nonsimple cysts were 24.2 +/- 11.6%, 5.7 +/- 6.3% for fibroadenomas, and 3.8 +/- 2.9 % for cancers (p < 0.05). Some of the cysts appeared smaller in DCC images than gray-scale images. These encouraging results demonstrate that characterization of nonsimple breast cysts may be improved by using DCC values from 2D elastography, which could potentially change management options of these cysts from intervention to imaging follow-up. A dedicated clinical trial to fully assess the efficacy of this technique is recommended.

Breast lesions: imaging with contrast-enhanced subharmonic US--initial experience.

PURPOSE: To prospectively compare accuracy of gray-scale subharmonic imaging (SHI) with that of standard gray-scale ultrasonography (US), power Doppler US (with and without contrast material), and mammography for the diagnosis of breast cancer, with histopathologic or clinical follow-up results as the reference standard. MATERIALS AND METHODS: This HIPAA-compliant pilot study had institutional review board approval; all subjects gave written informed consent. Fourteen women (age range, 37-66 years) had 16 biopsy-proved breast lesions. In SHI, pulses are transmitted at one frequency, but only echoes at half that frequency (the subharmonic) are received. A US scanner was modified to perform gray-scale SHI (transmitting at 4.4 and receiving at 2.2 MHz). Precontrast imaging (gray-scale US and power Doppler) was followed by contrast material-enhanced power Doppler and gray-scale SHI. A reader blinded to mammographic and pathologic findings assessed diagnosis on a six-point scale. Sensitivity, specificity, accuracy, and receiver operating characteristic (ROC) curves were computed for mammography, gray-scale and power Doppler imaging (pre- and postcontrast), and SHI. RESULTS: Of the 16 lesions, four (25%) were malignant. Mammography had 100% sensitivity and 20% specificity. Sensitivity and specificity, respectively, were 50% and 92% for precontrast imaging and 75% and 75% for contrast-enhanced power Doppler. SHI had 75% sensitivity and 83% specificity. Specificity was higher for all US modes than for mammography (P<.04). There were no significant differences in specificity among US modes or in sensitivity (P>or=.50). Area under the ROC curve for the diagnosis of breast cancer was 0.64 for standard gray-scale US and power Doppler US, 0.67 for contrast-enhanced power Doppler US, 0.76 for mammography, and 0.78 for SHI (P>.20). Contrast enhancement was better with SHI than with power Doppler (100% vs 44% of lesions with good or excellent enhancement; P=.004). CONCLUSION: SHI appears to improve the diagnosis of breast cancer relative to conventional US and mammography, albeit on the basis of results in a very limited number of subjects.

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 degrees-70 degrees and 110 degrees -140 degrees) with respect to the tube (orthogonal to the tube being 90 degrees). Volume data sets were obtained spanning 29 degrees lateral and 20 degrees 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 degrees) 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.

Vector Doppler imaging of a spinning disc ultrasound Doppler phantom.

Vector Doppler methods are used to obtain angle independent in-plane velocity information. Velocity magnitude as well as direction are reconstructed from regular steered colour flow and from split-aperture Doppler acquisitions. Spatially resolved in-plane velocity was obtained through Doppler colour flow mode and subsequent data triangulation. A depth-invariant constant Doppler angle was achieved by using a depth expanding transmit-receive Doppler aperture. Velocities of up to 50 cm s(-1) and 360 degrees vector velocity directions were measured. This was achieved by creating a spinning solid disc phantom. Such a phantom was built to allow underwater mounting and spinning of a solid disc-shaped ultrasound phantom (maximum velocity of 50 cm s-1). Doppler triangulation was realised by steered Doppler and by a split-aperture approach. Results of both imaging methods are shown. Split-aperture results showed errors of less then 10% for velocity magnitude estimation and less then 2.5 degrees for directional information.

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.

Real-time excitation-enhanced ultrasound contrast imaging.

A new nonlinear contrast specific imaging modality, excitation-enhanced imaging (EEI) has been implemented on commercially-available scanners for real-time imaging. This novel technique employs two acoustic fields: a low-frequency, high-intensity ultrasound field (the excitation field) to actively condition contrast microbubbles, and a second lower-intensity regular imaging field applied shortly afterwards to detect enhanced contrast scattering. A Logiq 9 scanner (GE Healthcare, Milwaukee, WI) with a 3.5C curved linear array and an AN2300 digital ultrasound engine (Analogic Corporation, Peabody, MA) with a P4-2 phased array transducer (Philips Medical Systems, Bothell, WA) were modified to perform EEI on a vector-by-vector basis in fundamental and pulse inversion harmonic grayscale modes. Ultrasound contrast microbubbles within an 8 mm vessel embedded in a tissue-mimicking flow phantom (ATS Laboratories, Bridgeport, CT) were imaged in vitro. While video intensities of scattered signals from the surrounding tissue were unchanged, video intensities of echoes from contrast bubbles within the vessel were markedly enhanced. The maximum enhancement achieved was 10.4 dB in harmonic mode (mean enhancement: 6.3 dB; p = 0.0007). In conclusion, EEI may improve the sensitivity of ultrasound contrast imaging, but further work is required to assess the in vivo potential of this new technique.