In many clinical conditions, such as head trauma, stroke, and low cardiac output states, the brain is at risk for hypoxic-ischemic injury. The metabolic rate and oxygen consumption of the brain are reflected in internal jugular venous oxygen saturation (sijvO2). The current gold standard for monitoring brain oxygenation is invasive; it requires jugular vein catheterization under fluoroscopic guidance and therefore is rarely used. Photoacoustic (PA) measurement, on the other hand, can estimate the oxygen consumption of the brain non-invasively in real time. Such a convenient method can potentially aid earlier detection and prevention of impending hypoxic brain injury. A dual-wavelength photoacoustic tomography (PAT) and ultrasound imaging (US) system was used to image the internal jugular vein (IJV) and estimate the sijvO2 in seven healthy volunteers. The system captured simultaneous co-registered PAT and US images at a rate of five frames per second. For each volunteer, the internal jugular vein was identified under ultrasound guidance, then, additional PA images from two optical wavelengths were collected and used to estimate the oxygen saturation of the internal jugular vein. For each volunteer, the oxygen saturation was calculated from transverse and longitudinal views of the internal jugular vein. The average sijvO2 was 72 +/- 7 %. The preliminary results are encouraging and agree with those reported in the literature. Photoacoustic images were successfully used to calculate the blood hemoglobin oxygen saturation in the internal jugular vein. These results raise confidence that this emerging technology can be used clinically for accurate, noninvasive estimation of sijvO2. In addition, the fast co-registration with US images makes the technique suitable for studying the temporal variations of oxygen saturation in response to physiologic challenges in clinical settings.

ABSTRACT:Nonalcoholic fatty liver disease (NAFLD) is a primary cause of parenchymal liver disease globally. There are currently several methods available to test the degree of steatosis in NAFLD patients, but all have drawbacks that limit their use.The objective of this study is to determine if a new technique, ultrasound (US) attenuation imaging (ATI), correlates with magnetic resonance proton density fat fraction imaging and hepatic echogenicity as seen on gray scale US imaging.Fifty-four patients were recruited at the University of Washington Medical Center from individuals who had already been scheduled for hepatic US or magnetic resonance imaging (MRI). All participants then underwent both hepatic MRI proton density fat fraction and US. Ultrasound images were then evaluated using ATI with 2 observers who individually determined relative grayscale echogenicity.Analysis showed positive correlation between ATI- and MRI-determined fat percentage in the case group (Spearman correlation: 0.50; P = 0.015). Furthermore, participants with NAFLD tended to have a higher ATI than controls (median: 0.70 vs 0.54 dB/cm/MHz; P < 0.001).This study demonstrates that US ATI combined with grayscale imaging is an effective way of assessing the degree of steatosis in patients with moderate to severe NAFLD.

PurposeTo assess diagnostic performance of quantitative ultrasound (QUS) biomarkers in assessing hepatic steatosis.MethodsWe prospectively recruited 125 participants (mean age 54 years) who underwent liver QUS, magnetic resonance imaging (MRI), and laboratory tests within 30 days in this IRB approved study. Based on MRI‐proton density fat fraction (MRI‐PDFF) and MRE, we divided 125 participants into normal liver, nonalcoholic fatty liver (NAFL) and liver fibrosis (≥F1) groups. We examined diagnostic performance of ultrasound attenuation coefficient (AC), normalized local variance (NLV), superb microvascular imaging‐based vascularity index (SMI‐VI), and shear wave velocity (SWV) for determining hepatic steatosis and fibrosis using area under receiver operating characteristic curve (AUC). We also analyzed correlations of QUS biomarkers to MRI using Spearman correlation coefficient.ResultsWe observed significant differences in AC, NLV, and SMI‐VI among the three groups (22 participants with normal liver, 78 with NAFL, and 25 with liver fibrosis). AUC of AC, NLV, and SMI‐VI for determining ≥ mild steatotic livers (MRI‐PDFF ≥5%) was 0.95, 0.90, and 0.92, respectively. AUC of SWV for determining ≥ F1 liver fibrosis was 0.93. The correlation of MRI‐PDFF was positive to AC (r = 0.91) and negative to NLV (r = −0.74), SMI‐VI (r = −0.8) in NAFL group. There was a significant difference in regression slope of AC to MRI‐PDFF in livers with and without ≥F1 (0.84 vs 0.91, P = .02).ConclusionsQUS biomarkers have high sensitivity and specificity to determine and grade hepatic steatosis and detect liver fibrosis. The effect of liver fibrosis on the performance of QUS biomarkers in quantifying liver fat content warrants further investigation.

ObjectivesTo quantify the bias of shear wave speed (SWS) measurements between different commercial ultrasonic shear elasticity systems and a magnetic resonance elastography (MRE) system in elastic and viscoelastic phantoms.MethodsTwo elastic phantoms, representing healthy through fibrotic liver, were measured with 5 different ultrasound platforms, and 3 viscoelastic phantoms, representing healthy through fibrotic liver tissue, were measured with 12 different ultrasound platforms. Measurements were performed with different systems at different sites, at 3 focal depths, and with different appraisers. The SWS bias across the systems was quantified as a function of the system, site, focal depth, and appraiser. A single MRE research system was also used to characterize these phantoms using discrete frequencies from 60 to 500 Hz.ResultsThe SWS from different systems had mean difference 95% confidence intervals of ±0.145 m/s (±9.6%) across both elastic phantoms and ± 0.340 m/s (±15.3%) across the viscoelastic phantoms. The focal depth and appraiser were less significant sources of SWS variability than the system and site. Magnetic resonance elastography best matched the ultrasonic SWS in the viscoelastic phantoms using a 140 Hz source but had a − 0.27 ± 0.027‐m/s (−12.2% ± 1.2%) bias when using the clinically implemented 60‐Hz vibration source.ConclusionsShear wave speed reconstruction across different manufacturer systems is more consistent in elastic than viscoelastic phantoms, with a mean difference bias of < ±10% in all cases. Magnetic resonance elastographic measurements in the elastic and viscoelastic phantoms best match the ultrasound systems with a 140‐Hz excitation but have a significant negative bias operating at 60 Hz. This study establishes a foundation for meaningful comparison of SWS measurements made with different platforms.

Aim of the study To assess the effect of water intake on ultrasound tissue characteristics and hemodynamics of adult livers. Material and methods In February 2020, we prospectively performed ultrasound shear wave elastography and attenuation imaging (ATI) of the liver parenchyma, and spectral Doppler sonography of the portal vein and hepatic artery in 19 adult healthy volunteers (10 men and 9 women, mean age 27 years, mean body mass index 24.65 kg/m2). We measured liver shear wave velocity (SWV, m/s), shear wave dispersion (SWD, m/s/kHz), attenuation coefficient (dB/cm/MHz), main portal vein velocity (PVV, cm/s), hepatic artery peak systolic velocity (PSV, cm/s), and end diastolic velocity (EDV, cm/s) immediately before and at different time points (15, 30, 45, and 60 minutes) after water intake (1.0 l water and 1.5 l water for body weight < 150 lbs. and ≥ 150 lbs., respectively). Results The differences in SWV, PVV, hepatic artery PSV and EDV before and after water intake were significant (p < 0.01) whereas the differences in SWD and ATI were not (p > 0.05) based on repeated measures ANOVA tests. The values of SWV, PVV, PSV, and EDV reached a peak at 30-45 minutes and returned to baseline 60 minutes after water intake. We observed positive correlations of SWV with PVV, PSV, and EDV in linear regression analyses (r2 > 0.73). Conclusions Water intake affects the liver stiffness and hemodynamics. No water intake at least one hour prior to liver ultrasound elastography and Doppler sonography is recommended.

Background Quantitative blood flow (QBF) measurements that use pulsed-wave US rely on difficult-to-meet conditions. Imaging biomarkers need to be quantitative and user and machine independent. Surrogate markers (eg, resistive index) fail to quantify actual volumetric flow. Standardization is possible, but relies on collaboration between users, manufacturers, and the U.S. Food and Drug Administration. Purpose To evaluate a Quantitative Imaging Biomarkers Alliance-supported, user- and machine-independent US method for quantitatively measuring QBF. Materials and Methods In this prospective study (March 2017 to March 2019), three different clinical US scanners were used to benchmark QBF in a calibrated flow phantom at three different laboratories each. Testing conditions involved changes in flow rate (1-12 mL/sec), imaging depth (2.5-7 cm), color flow gain (0%-100%), and flow past a stenosis. Each condition was performed under constant and pulsatile flow at 60 beats per minute, thus yielding eight distinct testing conditions. QBF was computed from three-dimensional color flow velocity, power, and scan geometry by using Gauss theorem. Statistical analysis was performed between systems and between laboratories. Systems and laboratories were anonymized when reporting results. Results For systems 1, 2, and 3, flow rate for constant and pulsatile flow was measured, respectively, with biases of 3.5% and 24.9%, 3.0% and 2.1%, and -22.1% and -10.9%. Coefficients of variation were 6.9% and 7.7%, 3.3% and 8.2%, and 9.6% and 17.3%, respectively. For changes in imaging depth, biases were 3.7% and 27.2%, -2.0% and -0.9%, and -22.8% and -5.9%, respectively. Respective coefficients of variation were 10.0% and 9.2%, 4.6% and 6.9%, and 10.1% and 11.6%. For changes in color flow gain, biases after filling the lumen with color pixels were 6.3% and 18.5%, 8.5% and 9.0%, and 16.6% and 6.2%, respectively. Respective coefficients of variation were 10.8% and 4.3%, 7.3% and 6.7%, and 6.7% and 5.3%. Poststenotic flow biases were 1.8% and 31.2%, 5.7% and -3.1%, and -18.3% and -18.2%, respectively. Conclusion Interlaboratory bias and variation of US-derived quantitative blood flow indicated its potential to become a clinical biomarker for the blood supply to end organs. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Forsberg in this issue.

Purpose: The aim of the study was to compare Superb Microvascular Imaging (SMI) to conventional color Doppler ultrasonography (CDUS) and power Doppler ultrasonography (PDUS) in depicting kidney cortical microvasculature. Methods: Using 3.5 MHz curve-linear array ultrasound transducer and manufacturer recommended color Doppler settings (Canon Medical Systems) for KIDNEY sonography, we performed kidney CDUS, PDUS, and SMI in 20 healthy adults (10 man and 10 women, mean age 27 years). Color Doppler signals in all color Doppler images were quantified by counting color pixel intensity, calculating area ratio of color to total region of interest (AR), and measuring distance of cortical end vessel to the kidney capsule. We used one-way analysis of variance (ANOVA) and post-hoc to test the difference in color pixel intensity, AR, and distance of cortical end vessel to the kidney capsule among SMI, CDUS, and PDUS and in all paired groups. Results: The differences in color pixel intensity, AR, and distance of cortical end vessel to the kidney capsule were significant among CDUS, PDUS, and SMI, as well as in all paired groups (P < 0.001). Color pixel intensity and AR in SMI were significantly higher than CDUS and PDUS (p < 0.001). The distance of cortical end vessel to the kidney capsule in SMI was significantly less than in CDUS and PDUS (p < 0.001). Inter- and intra-observer reliability of quantifying color Doppler images was good (Intraclass correlation coefficient: 0.79-0.92). Conclusion: Our results suggest that SMI seems more sensitive than CDUS and PDUS in depicting kidney cortical microvasculature.

ObjectivesThe purpose of this study was to compare Superb Microvascular Imaging (SMI; Toshiba America Medical Systems, Tustin, CA) with conventional color flow Doppler (CFD) and power Doppler (PD) imaging in the liver to distinguish between malignant and benign liver neoplasms.MethodsAfter Institutional Review Board approval (number 449984‐ED), patients undergoing routine pre–radiofrequency ablation planning ultrasound examinations for suspected hepatocellular carcinomas (HCCs) of less than 2 cm in diameter between January 1, 2015, and July 1, 2016, were prospectively identified. Four readers reviewed the ultrasound images independently for the presence or absence of flow centrally and along the periphery of the lesion.ResultsHigher peripheral vessel grades were found on SMI than CFD (P < .001) and PD (P < .001) imaging: in particular, more grade 2 (39% versus 16% and 11%, respectively) and grade 3 (8% versus 0% and 0%). Overall, more central and peripheral vessels were found on SMI than CFD and PD imaging for both HCC lesions (P < .001) and benign lesions (P < .001). Vascular grades were significantly higher in HCC lesions than benign lesions in nearly all cases, although the corresponding area under the curve values were relatively low, at 0.54 to 0.59 for the central vessel grades and 0.63 to 0.64 for the peripheral vessel grades.ConclusionsMore central and peripheral vessels were found around liver lesions on SMI than on CFD and PD imaging. Although there was significantly more vascularity on the periphery of malignant liver lesions than benign lesions, the overall diagnostic performance based on this criterion alone was relatively low, with an area under the curve of 0.64.

In this article, we describe our experience with shear wave propagation imaging (SWPI) as an adjunct to 2-dimensional (2D) shear wave elastography (SWE) in a cohort of patients being evaluated for diffuse liver disease. Two-dimensional SWE has been extensively studied in previous publications; however, 2D SWE using propagation images has not been widely described in the literature to date. We observed that when certain artifacts occurred on the color elastograms, highly characteristic changes to shear wave propagation contours were seen, which can help clarify the cause of the artifacts. To our knowledge, the use of SWPI to explain the etiology of artifacts has never been published before. The artifacts described in this article include the capsule reverberation artifact, penetration limitation or dropout artifact, artifact due to blood vessels, shadowing artifact, tissue motion artifact, and near-field distortion/precompression artifact. Hence, the purpose of this article is to show examples of common artifacts seen on 2D SWE as depicted on corresponding SWPI to demonstrate that both types of image displays are complementary to each other.

The detection of regional lymph node metastases is important in cancer staging as it guides the prognosis of the patient and the strategy for treatment. Sentinel lymph node biopsy (SLNB) is an accurate, less invasive alternative to axillary lymph node dissection. The sentinel lymph node hypothesis states that the pathological status of the axilla can be accurately predicted by determining the status of the first lymph nodes that drain from the primary tumor. Physicians use radio-labeled sulfur colloid and/or methylene blue dye to identify the SLN, which is most likely to contain metastatic cancer cells. However, the surgical procedure causes morbidity and associated expenses. To overcome these limitations, we developed a dual-modality photoacoustic and ultrasonic imaging system to noninvasively detect SLNs based on the accumulation of methylene blue dye. Ultimately, we aim to guide percutaneous needle biopsies and provide a minimally invasive method for axillary staging of breast cancer.

Many breast cancer patients receive neoadjuvant treatment to reduce tumor size and enable breast conserving therapy. Most imaging methods used to monitor response to neoadjuvant chemotherapy or hormone therapy depend on overall gross tumor morphology and size measurements, which may not be sensitive or specific, despite tumor response on a cellular level. A more sensitive and specific method of detecting response to therapy might allow earlier adjustments in treatment, and thus result in better outcomes while avoiding unnecessary morbidity. We developed an imaging system that combines spectral photoacoustic tomography and ultrasonography to predict breast neoadjuvant therapeutic response based on blood volume and blood oxygenation contrast. The system consists of a tunable dye laser pumped by a Nd:YAG laser, a commercial ultrasound imaging system (Philips iU22), and a multichannel data acquisition system which displays co-registered photoacoustic and ultrasound images in real time. Early studies demonstrate functional imaging capabilities, such as oxygen saturation and total concentration of hemoglobin, in addition to ultrasonography of tumor morphology. Further study is needed to determine if the co-registered photoacoustic tomography and ultrasonography system may provide an accurate tool to assess treatment efficacy by monitoring tumor response in vivo.

The metabolic rate and oxygen consumption of the brain is reflected in jugular venous oxygen saturation. In many clinical conditions, such as head trauma, stroke, and low cardiac output states, the brain is at risk for hypoxic-ischemic injury. The current gold standard for monitoring brain oxygenation is invasive and requires jugular vein catheterization under fluoroscopic guidance; and therefore it is rarely used. Photo-acoustic tomography in combination with ultrasound can be used to estimate oxygen saturation of the internal jugular vein in real-time. This noninvasive method will enable earlier detection and prevention of impending hypoxic brain injury. A wavelength-tunable dye laser pumped by a Nd:YAG laser delivers light through an optical fiber bundle, and a modified commercial ultrasound imaging system (Philips iU22) detects both the pulse-echo ultrasound (US) and photoacoustic (PA) signals. A custom-built multichannel data acquisition system renders co-registered ultrasound and photoacoustic images at 5 frames per second. After the jugular vein was localized in healthy volunteers, dual-wavelength PA images were used to calculate the blood hemoglobin oxygen saturation from the internal jugular vein in vivo. The preliminary results raise confidence that this emerging technology can be used clinically as an accurate, noninvasive indicator of cerebral oxygenation.

Sentinel lymph node biopsy (SLNB) has emerged as an accurate, less invasive alternative to axillary lymph node dissection, and it has rapidly become the standard of care for patients with clinically node-negative breast cancer. The sentinel lymph node (SLN) hypothesis states that the pathological status of the axilla can be accurately predicted by determining the status of the first (i.e., sentinel) lymph nodes that drain from the primary tumor. Physicians use radio-labeled sulfur colloid and/or methylene blue dye to identify the SLN, which is most likely to contain metastatic cancer cells. However, the surgical procedure causes morbidity and associated expenses. To overcome these limitations, we developed a dual-modality photoacoustic and ultrasound imaging system to noninvasively detect SLNs based on the accumulation of methylene blue dye. Ultimately, we aim to guide percutaneous needle biopsies and provide a minimally invasive method for axillary staging of breast cancer. The system consists of a tunable dye laser pumped by a Nd:YAG laser, a commercial ultrasound imaging system (Philips iU22), and a multichannel data acquisition system which displays co-registered photoacoustic and ultrasound images in real-time. Our clinical results demonstrate that real-time photoacoustic imaging can provide sensitive and specific detection of methylene blue dye in vivo. While preliminary studies have shown that in vivo detection of SLNs by using co-registered photoacoustic and ultrasound imaging is feasible, further investigation is needed to demonstrate robust SLN detection.

Selon la presente invention, un dispositif d'imagerie medicale photoacoustique comprend un ensemble conversion de longueur d'onde (108) configure pour delivrer en sortie des impulsions laser a une longueur d'onde ciblee. Il comprend egalement une sonde photoacoustique configuree pour couplage acoustique a un patient, pour direction des impulsions et pour acquisition, en reponse, de donnees de radiofrequence pour imagerie photoacoustique. Il peut comprendre un faisceau de fibres optiques (120) qui comprend une fibre optique ayant une extremite d'entree et peut etre configure pour eclairage, avec un faisceau homogene, de maniere a se conformer a un angle d'admission (160) de la fibre au niveau de cette extremite. Il peut egalement comprendre un collimateur de lumiere et un diffuseur pour reception des impulsions laser delivrees en sortie provenant du collimateur. Le diffuseur peut etre configure pour diffusion d'un foyer de la lumiere pulsee (148) sur une ouverture d'entree du faisceau pour egaliser la lumiere recue par differentes fibres optiques constitutives du faisceau. L'ensemble peut comprendre une cellule a colorants (132) et peut resider dans le dispositif.

We developed a novel trimodality system for human breast imaging by integrating photoacoustic (PA) and thermoacoustic (TA) imaging techniques into a modified commercial ultrasound scanner. Because light was delivered with an optical assembly placed within the microwave antenna, no mechanical switching between the microwave and laser sources was needed. Laser and microwave excitation pulses were interleaved to enable PA and TA data acquisition in parallel at a rate of 10 frames per second. A tube (7 mm inner diameter) filled with oxygenated bovine blood or 30 mM methylene blue dye was successfully detected in PA images in chicken breast tissue at depths of 6.6 and 8.4 cm, respectively, for the first time. The SNRs at these depths reached ∼24 and ∼15 dB, respectively, by averaging 200 signal acquisitions. Similarly, a tube (13 mm inner diameter) filled with saline solution (0.9%) at a depth of 4.4 cm in porcine fat tissue was successfully detected in TA images. The PA axial, lateral, and elevational resolutions were 640 μm, 720 μm, and 3.5 mm, respectively, suitable for breast cancer imaging. A PA noise-equivalent sensitivity to methylene blue solution of 260 nM was achieved in chicken tissue at a depth of 3.4 cm.

Identification of cancer cells in the lymph nodes surrounding a tumor is important in establishing prognosis. Optical detection techniques such as fluorescence and photoacoustic tomography (PAT) have been reported in preclinical studies for noninvasive sentinel lymph node (SLN) mapping. A method for validation of these techniques is needed for clinical trials. We report the use of a multimodal optical-radionuclear contrast agent as a validation tool for PAT in a preclinical model. Methylene blue (MB) was radiolabeled with 125I for multimodal SLN mapping and used in conjunction with MB to assess the feasibility of multimodal SLN mapping in a rat model by PAT and SPECT. MB provided sufficient contrast for identifying SLNs non-invasively with a PAT system adapted from a clinical ultrasound imaging system. The signal location was corroborated by SPECT using 125I labeled MB. The translation of PAT into the clinic can be facilitated by direct comparison with established imaging methods using a clinically relevant dual SPECT and photoacoustic imaging agent. The new high resolution PAT is a promising technology for sensitive and accurate SLN detection in cancer patients.