Papers by Flemming Forsberg
Ultrasound in Medicine & Biology, 2012
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… and Frequency Control, …, Jan 1, 1999
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PURPOSE/AIM Differential harmonic tissue imaging (dHTI) is a modern nonlinear sonographic imaging... more PURPOSE/AIM Differential harmonic tissue imaging (dHTI) is a modern nonlinear sonographic imaging technology designed to combine the advantages of gray scale ultrasonography and conventional harmonic tissue imaging. The exhibition will explain the physical principles of dTHI to radiologists in simple language with figures, schematic diagrams and the clinical applications of dTHI. CONTENT ORGANIZATION • Background of harmonic tissue imaging. • Describing the concepts of fundamental frequency, harmonic frequency, differential frequencies, pulse inversion and cancellation of fundamental signals by pulse subtraction. • Explaining image generation process. • Discuss different harmonic tissue imaging methods: a. Conventional tissue harmonic imaging. b. Pulse inversion harmonic imaging. c. Differential tissue harmonic imaging. • Discuss the advantages of disadvantages of tissue harmonic imaging compared with grey scale imaging. • Discuss the advantages and limitations of the various harmon...
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PURPOSE To compare contrast-enhanced subharmonic ultrasound imaging (SHI) of breast tumor neovasc... more PURPOSE To compare contrast-enhanced subharmonic ultrasound imaging (SHI) of breast tumor neovascularity to three immunohistochemical markers of angiogenesis in nude rats. METHOD AND MATERIALS Seventy athymic, nude, female rats were implanted with 5 x 106 breast cancer cells (MDA-MB-231) in the mammary fat pad. The contrast agent Definity (Lantheus Medical Imaging, N Billerica, MA) was injected in a tail vein (dose: 36 μl) and fundamental ultrasound imaging as well as pulse-inversion SHI was performed in triplicate with a modified Sonix RP scanner (Ultrasonix Imaging, Richmond, BC, Canada) using a L9-4 linear array (transmitting at 8 MHz and receiving at 4 MHz in SHI mode). Studies were performed 21, 24 and 28 days post implantation (based on our prior experience). After the experiments, specimens were stained for endothelial cells (CD31), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2). Fractional tumor vascularity (FV) was calculated from digital images as ...
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2012 IEEE International Ultrasonics Symposium, 2012
ABSTRACT Lymph node dissection is a widely used surgical procedure to treat and stage metastatic ... more ABSTRACT Lymph node dissection is a widely used surgical procedure to treat and stage metastatic lymph nodes but has substantial side effects, such as lymphedema. Histotripsy is a noninvasive ultrasonic therapy that creates well-demarcated tissue fractionation using high-pressure and short acoustic shockwave pulses. This study investigates the possibility using of histotripsy to ablate lymph nodes noninvasively. Experiments were performed on 6 mixed breed healthy pigs, 11-12 weeks old and weighing 31-43 kg. Their superficial inguinal lymph nodes were treated in vivo with 5- or 10-cycle histotripsy pulses generated by focused, 1MHz therapy transducers, delivered at 50Hz pulse repetition frequency and peak rarefaction pressure above 21MPa. The treatment was guided by ultrasound imaging probes (either ATL CL15-7 or ATL L12-5) with a commercial ultrasound imaging system, HDI 5000. In one selected case, contrast-specific ultrasound was performed after perimammary injection of Sonazoid (GE Healthcare, Oslo, Norway) to localize the lymph nodes. Anatomical landmarks were then used to identify the same nodes for targeted therapy. The histological results show that, after histotripsy treatment, only the targeted lymph nodes were affected and they had demarcated foci of necrosis with minimal damage to the adjacent and intervening tissue. This in vivo acute study demonstrates the capability of histotripsy to noninvasively generate tissue fractionation within targeted lymph nodes, suggesting that histotripsy has the potential in noninvasive lymph node ablation.
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PURPOSE To investigate the feasibility of using high frequency subharmonic aided pressure estimat... more PURPOSE To investigate the feasibility of using high frequency subharmonic aided pressure estimation (SHAPE; U.S. patent 6,302,845) as a noninvasive alternative for monitoring of interstitial fluid pressures (IFP) measurements within locally advanced breast cancer an initial in vitro study was conducted. METHOD AND MATERIALS In vitro SHAPE with 3 different contrast agents; Definity (Lantheus Medical Imaging, N Billerica, MA), QFX (Nanfang Hospital, Guangzhou, China) and Sonazoid (GE Healthcare, Oslo, Norway) were compared. Pressure within a water-tank was measured with a pulse-echo system consisting of 2 confocally positioned single-element transducers and monitored with a pressure gauge. A programmable function generator (8116A; Hewlett Packard, Santa Clara, CA) produced pulses (64 cycles, 5 Hz PRF) that were amplified in a broadband 50dB RF power amplifier (3100LA; ENI, Rochester NY) before being supplied to the transmitting transducer. The transmitted signal was sent at a frequen...
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PURPOSE Ambient pressure changes affect the subharmonic signals from ultrasound (US) contrast mic... more PURPOSE Ambient pressure changes affect the subharmonic signals from ultrasound (US) contrast microbubbles. We have proposed subharmonic aided pressure estimation (SHAPE; U.S. patent 6,302,845) and in this study implemented real-time SHAPE on a commercial US scanner. METHOD AND MATERIALS An experimental pulse-echo system for SHAPE was constructed based on two single element transducers assembled confocally at a 60º angle to each other. A transducer with a bandwidth of 38 % and a center frequency of 2.2 MHz (Staveley, East Hartford, CT) was used as the transmitter and a second transducer with a bandwidth of 86 % and a center frequency of 3.6 MHz (Etalon Inc., Lebanon, IN) was used as the receiver. Changes in the first, second, and subharmonic amplitudes of 6 different US contrast agents were measured in vitro at hydrostatic pressures from 0-186 mmHg, acoustic pressures from 0.35-0.60 MPa and frequencies of 2.5-6.6 MHz. The optimal parameters for SHAPE (i.e., highest sensitivity) were...
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PURPOSE Advances in processing techniques for diagnostic subharmonic imaging (at half the insonat... more PURPOSE Advances in processing techniques for diagnostic subharmonic imaging (at half the insonation frequency) using ultrasound (US) contrast agents are ongoing. Ambient pressure sensitivity of the scattered subharmonic signals from these microbubbles can be utilized to track in vivo pressures, but the best processing technique for this application has yet to be established. METHOD AND MATERIALS Unprocessed RF data using SonixRP scanner (Ultrasonix, Richmond, BC, Canada) and simultaneous ambient pressures using a 5F solid state catheter tip Millar manometer were obtained from lumen of a 4 mm diameter vessel in a Doppler flow phantom (ATS Laboratories Inc., Bridgeport, CT), part of a closed loop flow system. Transmit parameters were 2.5 MHz and 0.22 MPa to elicit subharmonic response from Sonazoid microbubbles (GE Healthcare, Oslo, Norway) at 1.25 MHz (in the ambient pressure sensitive phase of the subharmonic emissions). Four techniques (mean signal in 16 % and 40 % bandwidth (BW) ...
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PURPOSE Hepatic vein pressure gradient (HVPG) data is clinically useful in the management of cirr... more PURPOSE Hepatic vein pressure gradient (HVPG) data is clinically useful in the management of cirrhosis and other liver diseases. Unfortunately, current HPVG measurements are either invasive catheter based measurements, or noninvasive but indirect and qualitative imaging approaches. Our group has previously shown the subharmonic amplitude of microbubble-based ultrasound contrast agents to be a good indicator of hydrostatic pressure (a technique known as SHAPE). Here, we present preliminary results from a first in humans, SHAPE study for the measurement of portal hypertension. METHOD AND MATERIALS Following transjugular liver biopsy, 16 patients received a co-infusion of Sonazoid (0.72 μL microbubbles/kg/hour; GE Healthcare, Oslo, Norway) and saline (120 ml/hour). Subjects were scanned with a modified Logiq 9 scanner (GE Healthcare, Milwaukee, WI) with a 4C curvilinear probe. The acoustic output for optimal SHAPE sensitivity (the point of maximal change in subharmonic amplitude as a f...
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CONCLUSION The developed Breast Ultrasound diagnostic tool performed exceedingly well in two inde... more CONCLUSION The developed Breast Ultrasound diagnostic tool performed exceedingly well in two independent “stress test” evaluations. BC application promises to reduce well-known variability of radiologists, increase overall accuracy of reading performance by using a more structured protocol and flow, and therefore create an environment that would lead to substantial reduction in the number of biopsies for benign masses (reduction of False Positives) BACKGROUND Breast Companion® (BC) is diagnostic tool that assists radiologists in their interpretation during BI-RADS assessment. BC has been extensively validated for diagnostic breast sonography. As part of clinical utility valuation two luminary institutions (TJU & UCSD) completed an independent "stress test" evaluation of the tool performance and its improvement of the existing reading practice EVALUATION BC utility was valuated using "stress test" cohorts retrieved from the database of confirmed cases. The 1st coh...
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BioMed research international, 2015
Nonlinear contrast-enhanced ultrasound imaging schemes strive to suppress tissue signals in order... more Nonlinear contrast-enhanced ultrasound imaging schemes strive to suppress tissue signals in order to better visualize nonlinear signals from blood-pooling ultrasound contrast agents. Because tissue does not generate a subharmonic response (i.e., signal at half the transmit frequency), subharmonic imaging has been proposed as a method for isolating ultrasound microbubble signals while suppressing surrounding tissue signals. In this paper, we summarize recent advances in the use of subharmonic imaging in vivo. These advances include the implementation of subharmonic imaging on linear and curvilinear arrays, intravascular probes, and three-dimensional probes for breast, renal, liver, plaque, and tumor imaging.
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2007 IEEE Ultrasonics Symposium Proceedings, 2007
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PURPOSE To determine if M-mode or Shear Wave Elasticity (SWE) imaging (independently or combined)... more PURPOSE To determine if M-mode or Shear Wave Elasticity (SWE) imaging (independently or combined) provide quantitative markers of liver fibrosis compared to conventional grayscale ultrasound (US) imaging and pathology (the reference standard). METHOD AND MATERIALS Twelve subjects scheduled for an US-guided liver biopsy and 5 healthy volunteers were scanned with a broad bandwidth curvi-linear array using an IU22 (Philips Medical Systems, Bothell, WA; for grayscale and M-mode imaging) and an Aixplorer scanner (SuperSonic Imagine, Aix-en-Provence, France; for SWE imaging). The M-mode images were quantified using the scanners’ existing calculation software package and by a novel algorithm (implemented in Matlab; Mathworks, Natick, MA) extracting distances between lines of similar intensities (L2LD) as a quantitative biomarker of liver status. Liver stiffness (in kPa) was recorded from the SWE images, while a radiologist (blinded to the other results) scored the grayscale US for degree o...
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Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine, 2011
Parametric maps showing perfusion of contrast media can be useful tools for characterizing lesion... more 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 detect...
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Ultrasound quarterly, Jan 18, 2015
To evaluate the flow imaging capabilities of a new prototype ultrasound (US) image processing tec... more To evaluate the flow imaging capabilities of a new prototype ultrasound (US) image processing technique (superb micro-vascular imaging [SMI]; Toshiba Medical Systems, Tokyo, Japan) for depiction of microvascular flow in normal thyroid tissue and thyroid nodules compared with standard color and power Doppler US imaging.Ten healthy volunteers and 22 patients, with a total of 25 thyroid nodules, scheduled for US-guided fine needle aspiration were enrolled in this prospective study. Subjects underwent US examination consisting of grayscale, color and power Doppler imaging (CDI and PDI) followed by color and monochrome SMI and pulsed Doppler. SMI is a novel, microvascular flow imaging mode implemented on the Aplio 500 US system (Toshiba). SMI uses advanced clutter suppression to extract flow signals from large to small vessels and depicts this information at high frame rates as a color overlay image or as a monochrome map of flow. Two radiologists independently scored still images and di...
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Academic radiology, Jan 13, 2015
The objective of this study was to evaluate and compare contrast-enhanced subharmonic and harmoni... more The objective of this study was to evaluate and compare contrast-enhanced subharmonic and harmonic ultrasound as tools for characterizing solid renal masses and monitoring their response to cryoablation therapy. Sixteen patients undergoing percutaneous ablation of a renal mass provided informed consent to undergo ultrasound examinations the morning before and approximately 4 months after cryoablation. Ultrasound contrast parameters during pretreatment imaging were compared to biopsy results obtained during ablation (n = 13). Posttreatment changes were evaluated by a radiologist and compared to contrast-enhanced magnetic resonance imaging (MRI)/computed tomography (CT) follow-up. All masses initially showed heterogeneous enhancement with both subharmonic and harmonic ultrasound. Early contrast washout in the mass relative to the cortex was observed in 6 of 9 malignant and 0 of 4 benign lesions in subharmonic mode and 8 of 9 malignant and 1 of 4 benign lesions in harmonic imaging. In ...
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PURPOSE To compare peak systolic velocities (PSVs) and degree of stenoses obtained with a novel, ... more PURPOSE To compare peak systolic velocities (PSVs) and degree of stenoses obtained with a novel, real time three-dimensional (i.e., 4D) Doppler ultrasound (US)scanner (the Encore PV; Vuesonix Sensors, Wayne, PA) to conventional Doppler US of carotid arteries (common=CCA; internal=ICA; external=ECA). Also to assess Encore PV volume flow (VF) measurements. METHOD AND MATERIALS PSV of the CCA, ECA and ICA were obtained bilaterally in 70 patients referred for clinically indicated carotid US evaluations. The degree of stenosis in the ICA was also calculated based on the ICA PSV and on the ICA/CCA PSV ratio. In a subset of patients ICA stenosis was also assessed with MRA or CTA. The Encore PV, which detects all 3D blood flow velocity vectors within a volume, was used to obtain 10 s longitudinal volumes of the ICA, ECA and CCA. On the Encore PV, a reader determined the center line of the vessels and the PSV and VF were then automatically calculated. The error of the VF measurements was obt...
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IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, 2015
Ability to visualize breast lesion vascularity and quantify the vascular heterogeneity using cont... more Ability to visualize breast lesion vascularity and quantify the vascular heterogeneity using contrast-enhanced 3-D harmonic (HI) and subharmonic (SHI) ultrasound imaging was investigated in a clinical population. Patients (n = 134) identified with breast lesions on mammography were scanned using power Doppler imaging, contrast-enhanced 3-D HI, and 3-D SHI on a modified Logiq 9 scanner (GE Healthcare). A region of interest corresponding to ultrasound contrast agent flow was identified in 4D View (GE Medical Systems) and mapped to raw slice data to generate a map of time-intensity curves for the lesion volume. Time points corresponding to baseline, peak intensity, and washout of ultrasound contrast agent were identified and used to generate and compare vascular heterogeneity plots for malignant and benign lesions. Vascularity was observed with power Doppler imaging in 84 lesions (63 benign and 21 malignant). The 3-D HI showed flow in 8 lesions (5 benign and 3 malignant), whereas 3-D SHI visualized flow in 68 lesions (49 benign and 19 malignant). Analysis of vascular heterogeneity in the 3-D SHI volumes found benign lesions having a significant difference in vascularity between central and peripheral sections (1.71 ± 0.96 vs. 1.13 ± 0.79 dB, p < 0.001, respectively), whereas malignant lesions showed no difference (1.66 ± 1.39 vs. 1.24 ± 1.14 dB, p = 0.24), indicative of more vascular coverage. These preliminary results suggest quantitative evaluation of vascular heterogeneity in breast lesions using contrast-enhanced 3-D SHI is feasible and able to detect variations in vascularity between central and peripheral sections for benign and malignant lesions.
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Ultrasound in medicine & biology, 2009
The aim of this study was to develop a novel automated motion compensation algorithm for producin... more The aim of this study was to develop a novel automated motion compensation algorithm for producing cumulative maximum intensity (CMI) images from subharmonic imaging (SHI) of breast lesions. SHI is a nonlinear contrast-specific ultrasound imaging technique in which pulses are received at half the frequency of the transmitted pulses. A Logiq 9 scanner (GE Healthcare, Milwaukee, WI, USA) was modified to operate in grayscale SHI mode (transmitting/receiving at 4.4/2.2 MHz) and used to scan 14 women with 16 breast lesions. Manual CMI images were reconstructed by temporal maximum-intensity projection of pixels traced from the first frame to the last. In the new automated technique, the user selects a kernel in the first frame and the algorithm then uses the sum of absolute difference (SAD) technique to identify motion-induced displacements in the remaining frames. A reliability parameter was used to estimate the accuracy of the motion tracking based on the ratio of the minimum SAD to the...
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Papers by Flemming Forsberg