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To minimize drug-related toxicity and monitor dosing regimens, an ultra-sensitive, simple and high-throughput analytical method for therapeutic drug monitoring is required. A novel LC-MS/MS bioassay of levetiracetam, lamotrigine and 10-hydroxycarbazepine in human plasma was established. The analytes were separated on a Hypersil GOLD™ CThis method can be used to monitor drug concentrations and decision-making in epileptic patients.

BACKGROUND AND OBJECTIVES We have developed a novel anti-vascular technique, termed photo-mediated ultrasound therapy (PUT), which utilizes nanosecond duration laser pulses synchronized with ultrasound bursts to remove the microvasculature through cavitation. The objective of the current study is to explore the potential of PUT in removing subcutaneous microvessels. STUDY DESIGN/MATERIALS AND METHODS The auricular blood vessels of two New Zealand white rabbits were treated by PUT with a peak negative ultrasound pressure of 0.45 MPa at 0.5 MHz, and a laser fluence of 0.056 J/cm2 at 1064 nm for 10 minutes. Blood perfusion in the treated area was measured by a commercial laser speckle imaging (LSI) system before and immediately after treatment, as well as at 1 hour, 3 days, 2 weeks, and 4 weeks post-treatment. Perfusion rates of 38 individual vessels from four rabbit ears were tracked during this time period for longitudinal assessment. RESULTS The measured perfusion rates of the vessels in the treated areas, as quantified by the relative change in perfusion rate, showed a statistically significant decrease for all time points post-treatment (P

Using data from a new hedge fund database, we examine the impact of social networks on the return comovement of stock hedge funds in China. We use structural holes in the college alumni networks of managers to measure the managers’ social network positions. We perform an empirical analysis on a sample of 3,012 hedge fund products in China from 2010 to 2017. We find that greater structural holes are associated with higher return comovement. The positive impact of the structural holes on return comovement is not affected by market cycles, a manager's major in college, or his or her abilities.

Photoacoustic microscopy (PAM) has great potential for visualization of the microvasculature with high spatial resolution and contrast. Early detection and differentiation of newly developed blood vessels named choroidal neovascularization (CNV) from normal vasculature remains a challenge in ophthalmology. Exogenous contrast agents can assist with improving PAM sensitivity, leading to differentiation of CNV. Here, an FDA-approved indocyanine green (ICG) was utilized as a PAM contrast agent. ICG was conjugated with RGD peptides, allowing the ICG to bind to the integrin expressed in CNV. Molecular PAM imaging showed that ICG-RGD can target CNV for up to 5 days post intravenous administration in living rabbits with a model of CNV. The PAM image sensitivity and image contrast were significantly enhanced by 15-fold at 24 h post-injection. Overall, the presented approach demonstrates the possibility of targeted ICG to be employed in PAM molecular imaging, allowing more precise evaluation of neovascularization. This article is protected by copyright. All rights reserved.

PURPOSE Transrectal ultrasound (TRUS)-guided biopsy is the standard procedure for evaluating the presence and aggressiveness of prostate cancer. TRUS biopsy involves tissue removal, and suffers from low core yield as well as high false negative rate. A less invasive and more accurate diagnostic procedure for prostate cancer is therefore highly desired. Combining the optical sensitivity and ultrasonic resolution to resolve the spatial distribution of the major molecular components in tissue, photoacoustic (PA) technology could be an alternative approach for the diagnosis of prostate cancer. The purpose of this study was to examine the feasibility of identifying aggressive prostate cancer using interstitial PA measurements. METHODS Seventeen patients with prebiopsy magnetic resonance imaging (MRI), TRUS biopsies, and planned prostatectomies were enrolled in this study. The interstitial PA measurements were achieved using our recently developed needle PA probe, which was inserted into the ex vivo prostates in the fashion of a biopsy needle. A total of 70 interstitial PA measurements were acquired. The PA measurements were quantified by a previously established PA physio-chemical analysis (PAPCA) method. The histology has confirmed the nonaggressive and aggressive cancerous conditions at the insertion locations. The diagnostic accuracy was also compared to that provided by the prebiopsy MRI. RESULTS The quantitative study shows significant differences between the individual parameters of the nonaggressive and the aggressive cancerous regions (P < 0.005). Multivariate analysis of the quantitative features achieved a diagnostic accuracy of 78.6% for differentiating nonaggressive and aggressive prostate cancer tissues. CONCLUSIONS The proposed procedure has shown promises in the diagnosis of aggressive prostate cancer.

Anastrozole is currently used as first-line treatment in locally advanced or metastatic breast cancer. A generic anastrozole tablet was developed to offer an alternative to the marketed tablet formulation. The aim of the current study was to evaluate the bioequivalence between the test and reference formulations of anastrozole in a single-dose, 2-period, 2-sequence crossover study with a 14-day washout interval. A total of 20 healthy male Chinese volunteers were enrolled and completed the study, after oral administration of a single dose of 1.0-mg test and reference formulations of anastrozole. The blood samples were collected at different times and were determined by a fully validated high-pressure liquid chromatography-tandem mass spectrometry method. The evaluated pharmacokinetic parameters, including Cmax , AUC0-t , and AUC0-∞ , were assessed for bioequivalence based on current guidelines. The observed pharmacokinetic parameters of anastrozole of the test drug were similar to those of the reference formulation. The 90% confidence intervals of test/reference ratios for Cmax , AUC0-t , and AUC0-∞ were within the bioequivalence acceptance range of 80%-125%. The results obtained from these healthy Chinese subjects in this study suggest that the test formulation of anastrozole 1.0-mg tablet is bioequivalent to the reference formulation (Arimidex 1.0-mg tablet).

Imatinib at 400 mg daily is the standard treatment for patients affected with CML and GIST. The intervariability in plasma concentration is very significant. In many reports, a good therapeutic effect is attributed to an adequate concentration of Imatinib. However, few studies have been conducted to investigate the association between plasma concentration and side effects. Besides, no upper concentration limit of Imatinib plasma concentration detection has been established. The correlation of Imatinib trough concentrations (Cmin) with adverse effects (AEs) was described here. Plasma samples were obtained from patients after 3 months treatment with Imatinib (steady state, n = 122). Liquid chromatography/ tandem mass spectrometry was used to determine the concentration of Imatinib and its metabolite NDI. The incidence of myelosuppression was increased significantly with the increased Imatinib trough plasma concentration. The plasma level of Imatinib and NDI in patients who developed myelosuppression are 1698.3 ± 598.6 ng/mL and 242.1 ng/mL, respectively, which were significantly higher than those in patients who did not (1327.2 ± 623.4 ng/mL, P = 1.75 × 10‐4; 206.3 ng/mL, P = 0.006). Estimated exposure thresholds of Imatinib and NDI were 1451.6 ng/mL with ROCAUC (95%CI) of 0.693 (0.597–0.789) and 207.1 ng/mL with ROCAUC (95%CI) of 0.646 (0.546–0.745), respectively. Multivariate regression confirmed the correlation of Imatinib Cmin with myelosuppression. Other side effects such as fluid retention and rash were not found to be correlated with Imatinib concentrations. These results suggest that trough concentration of Imatinib should be taken into consideration to increase the safety of Imatinib therapy in GIST patients.

Purpose The aim of this work was to experimentally demonstrate the feasibility of x-ray acoustic computed tomography (XACT) as a dosimetry tool in a clinical radiotherapy environment. Methods The acoustic waves induced following a single pulse of linear accelerator irradiation in a water tank were detected with an immersion ultrasound transducer. By rotating the collimator and keeping the transducer stationary, acoustic signals at varying angles surrounding the field were detected and reconstructed to form an XACT image. Simulated XACT images were obtained using a previously developed simulation workflow. Profiles extracted from experimental and simulated XACT images were compared to profiles measured with an ion chamber. A variety of radiation field sizes and shapes were investigated. Results XACT images resembling the geometry of the delivered radiation field were obtained for fields ranging from simple squares to more complex shapes. When comparing profiles extracted from simulated and experimental XACT images of a 4 cm × 4 cm field, 97% of points were found to pass a 3%/3 mm gamma test. Agreement between simulated and experimental XACT images worsened when comparing fields with fine details. Profiles extracted from experimental XACT images were compared to profiles obtained through clinical ion chamber measurements, confirming that the intensity of XACT images is related to deposited radiation dose. Seventy-seven percent of the points in a profile extracted from an experimental XACT image of a 4 cm × 4 cm field passed a 7%/4 mm gamma test when compared to an ion chamber measured profile. In a complicated puzzle-piece shaped field, 86% of the points in an XACT extracted profile passed a 7%/4 mm gamma test. Conclusions XACT images with intensity related to the spatial distribution of deposited dose in a water tank were formed for a variety of field sizes and shapes. XACT has the potential to be a useful tool for absolute, relative and in vivo dosimetry.

SummaryBackground Thiopurine-induced leukopenia is the most common dangerous adverse event in Asians. NUDT15 R139C was recently proposed to be a promising biomarker for leukopenia with thiopurine therapy in Asians, but this has not been replicated in the Chinese population. Aim To investigate the influence of NUDT15 R139C, thiopurine S-methyltransferase (TPMT), 6-TGN and 6-MMPR on thiopurine-induced leukopenia in Chinese patients with Crohn's disease. Methods Clinical and epidemiological characteristics were reviewed from medical records. NUDT15 R139C and TPMT were genotyped. 6-TGN/6-MMPR concentrations were measured with high-performance liquid chromatography (HPLC). Results A total of 253 patients were included, 65 (25.7%) of whom experienced leukopenia. The median follow-up with thiopurine treatment was 38.0 weeks (range, 1–192 weeks). NUDT15 R139C was strongly associated with the incidence of leukopenia (70.2% mutation vs. 12.8% wild type; P=8.61×10−19; odds ratio, 10.80; 95% CI, 5.89–19.83). However, TPMT genotype was not found to be correlated with the incidence of leukopenia (P = 0.44). In subgroup of NUDT15 wild type, there was significant difference of 6TGN concentration between patients with and without leukopenia (413.0 (174.2–831.4) vs. 279.7 (77.3–666.9) pmol/8 × 108 RBC, P = 0.0055). In contrast, no association was found in patients with NUDT15 R139C variant alleles (P = 0.26). 6-MMPR was not correlated with leukopenia (P = 0.84). Conclusions In Chinese patients, it is strongly recommended to detect NUDT15 genotype rather than TPMT before initiating thiopurine drugs. 6TGN concentration should be routinely monitored in CD patients with NUDT15 wild type. As for CT genotype, starting at low dose and careful monitoring for leukopenia and 6TGN levels is recommended.

A rapid and sensitive liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method to determine clonidine in human plasma was developed and fully validated. Sample preparation was involved an one-step extraction with diethyl ether. Donepezil was employed as the internal standard (IS). Chromatographic separation was performed on a Hypersil BDS C18 column (i.d. 2.1 × 50 mm, particle size 3μm) with a mobile phase of methanol-water (containing 0.1% formic acid; 60:40, v/v) at a flow rate of 200 μL/min. The peaks were detected by mass spectrometry using the electrospray ion source in selected reaction monitoring mode. The extraction recovery was 72.53-85.25%. The method was found to be linear in a concentration range of 0.02-6.00 ng/mL and the lower limit of quantification was 0.02 ng/mL. The within- and between-batch precisions at three concentrations were 4.33-16.47 and 7.24-17.24% with accuracies of -2.47-10.91 and 1.86-10.19%, respectively. This validated method was successfully used for a bioequivalence study of two clonidine transdermal patches on healthy volunteers. The results suggested that the test formulation of clonidine patch met the regulatory criterion for bioequivalence to the reference formulation, but a larger sample size should be needed for the estimation of bioequivalence.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Genetic polymorphisms of VKORC1 and CYP2C9 are known to influence warfarin dosage. * Recent studies among Caucasians showed that polymorphisms of CYP4F2 also play a role in warfarin pharmacogenetics. * The contribution of CYP4F2 variants to the variability inwarfarin dose requirement in Chinese subjects remains to be investigated. WHAT THIS STUDY ADDS * This research was to study the effect of CYP4F2 variants on warfarin requirements in the Han Chinese population. * This study developed a multiple regression model including CYP2C9, VKORC1 3673G>A, CYP4F2 genotypes and age, weight, combination use of amiodarone which could explain 56.1% of the individual variability in warfarin dose CYP4F2 could explain 4% of the variance in warfarin dose. * We found that one novel genotypic polymorphism 5417G>T for Asp36Tyr, which was identified as an important marker of warfarin resistance, was absent in the Han Chinese population in our study. AIMS The objective of this study was to assess the effect of the CYP4F2 on the daily stable warfarin dose requirement in Han Chinese patients with mechanical heart valve replacement (MHVR). METHODS From March 2007 to November 2008, 222 Han Chinese MHVR patients were recruited in our study. VKORC1 3673G>A, 5417G>T, CYP2C9*3 and CYP4F2 rs2108622 were genotyped by using the polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP). Polymorphisms of VKORC1 9041G>A were detected by direct sequencing. Multiple linear regression analysis was used to investigate the contribution of CYP4F2. RESULTS The CYP4F2 rs2108622 CT/TT group took a significantly higher stable warfarin dose (3.2 mg day(-1)) than the CC group (2.9 mg day(-1), 95% CI 0.2, 1.0, P= 0.033). The multiple linear regression model included VKORC1 3673G>A, CYP2C9, CYP4F2 genotypes and clinical characteristics. The model could explain 56.1% of the variance in stable warfarin dose in Han Chinese patients with MHVR. CYP4F2 contributed about 4% to the variance in the warfarin dose. There was no variation in the SNPs of VKORC1 5417G>T. CONCLUSION CYP4F2 is a minor significant factor of individual variability in the stable warfarin dose in Han Chinese patients with MHVR. The effect of CYP2C9 and VKORC1 genotypes on variability in the stable warfarin dose had also been confirmed.

Photoacoustic tomography (PAT), a nonionizing, noninvasive, laser-based technology was adapted to joint imaging for the first time. Pulsed laser light in the near-infrared region was directed toward a joint with resultant ultrasonic signals recorded and used to reconstruct images that present the optical properties in subsurface joint tissues. The feasibility of this joint imaging system was validated on a Sprague Dawley rat tail model and verified through comparison with histology. With sufficient penetration depth, PAT realized tomographic imaging of a joint as a whole organ noninvasively. Based on the optical contrast, various intra- and extra-articular tissues, including skin, fat, muscle, blood vessels, synovium and bone, were presented successfully in images with satisfactory spatial resolution that was primarily limited by the bandwidth of detected photoacoustic signals rather than optical diffusion as occurs in traditional optical imaging. PAT, with its intrinsic advantages, may provide a unique opportunity to enable the early diagnosis of inflammatory joint disorders, e.g., rheumatoid arthritis, and to monitor therapeutic outcomes with high sensitivity and accuracy.

Aim To improve and validate a more stable and less time-consuming method based on liquid chromatography and tandem mass spectrometry (LC- MS/MS) for the quantitative measurement of Imatinib and its metabolite N-demethyl-Imatinib (NDI) in human plasma. Methods Separation of analytes was performed on a Waters XTerra RP18 column (50mm×2.1 mm i.d., 3.5 μm) with a mobile phase consisting of methanol/acetonitrile/ water (65:20:15, v/v/v) with 0.05% formic acid at a flow-rate of 0.2 ml/min. The Quattro MicroTM triple quadruple mass spectrometer was operated in the multiple-reaction monitoring mode via positive electrospray ionization interface using the transition: m/z 494.0 → 394.0 for Imatinib, m/z 479.6 → 394.0 for NDI and m/z 488.2 → 394.0 for IS. Results The method was linear over 0.01–10 μg/mL for Imatinib and NDI. The intra- and inter-day precisions were all less than 15% in terms of relative standard deviation (RSD), and the accuracy was within ±15% in terms of relative error (RE) for both Imatinib and NDI. The lower limit of quantification (LLOQ) was identifiable and reproducible at 10 ng/mL. Conclusions The method was sensitive, specific and less time-consuming and it was successfully applied in GIST patients treated with Imatinib.

Purpose: X-ray acoustic computed tomography (XACT) is an emerging technique that images the dose deposited within an object following linac irradiation by detecting acoustic waves induced via the photoacoustic effect. This work shows that XACT images can be formed in soft-tissue equivalent material and that dosimetric information can be extracted from such images. Methods: Acoustic waves induced in a water tank following irradiation by a 10 MV flattening filter free photon beam were detected with an immersion ultrasound transducer at 60 angles surrounding the radiation field. A back-projection algorithm was used to reconstruct an XACT image from the detected transducer signals. Profiles extracted from XACT images were compared to profiles measured with ion chambers as per the current clinical protocol. Results: XACT images were successfully formed of simple 4 cm × 4 cm and 6 cm × 3 cm fields, as well as of more complicated multi-leaf collimator defined fields. For the 6 cm × 3 cm field, 74% and 87% of the XACT profile points in the 6 cm and 3 cm dimensions, respectively, passed a 7% / 4 mm gamma test when compared to ion chamber measurements. In a complicated puzzle piece shaped field, 86% of the pixels in an extracted profile passed a 7% / 4 mm gamma test. Conclusions: XACT is capable of imaging the dose distribution delivered by a variety of field sizes and shapes in water, and is a viable technique for both water tank and in vivo dosimetry.

Matrine and oxymatrine are the major bioactive compounds extracted from the root of Sophora flavescens Ait, which have been widely used in traditional Chinese medicines. The objective of the study was to investigate the effects of matrine or oxymatrine on hepatic cytochrome P450 (CYP450) and the underlying molecular mechanisms. Matrine (15, 75 and 150 mg/kg) or oxymatrine (36, 180 and 360 mg/kg) was administered to rats for 14 days and the activities of CYP450 were measured by the quantification of the metabolites from multiple CYP450 probe substrates, using validated liquid chromatography coupled with liquid chromatography-tandem mass spectrometry detection (LC-MS/MS) and high-performance liquid chromatography methods. The mRNA and protein expression levels of CYPs were determined by quantitative real-time reverse-transcription polymerase chain reaction and Western blotting analysis respectively. Interactions between matrine or oxymatrine and human constitutive androstane (CAR), pregnane X receptor were evaluated by means of the reporter gene assay in CV-1 cells. Our study showed that matrine and oxymatrine significantly induced the activity and gene expression of CYP2B1 in a dose-dependent manner; matrine (150 mg/kg) slightly induced the mRNA and protein expression of CYP2E1 and mildly inhibited the mRNA and protein expression of CYP3A1 in rats. Matrine or oxymatrine could activate human CAR and induce the CYP2B reporter construct in CV-1 cells. These results reveal that matrine and oxymatrine can induce the activity and expression of CYP2B1/2 in rats, and the underlying mechanism may be related to the activation of CAR.

A liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and validated for determining tacrolimus (FK506) in rat tissues to study the effect of Schisandra sphenanthera extract on FK506 tissue distribution. After a liquid-liquid extraction with ethyl acetate, FK506 and ascomycin (IS) were subjected to LC-MS/MS analysis using positive electrospray ionization under multiple reactions monitoring mode. Chromatographic separation of FK506 and ascomycin was achieved on a Hypersil BDS C(18) column with a mobile phase consisting of methanol-water (containing 2 mM ammonium acetate, 95 : 5, v/v). The intra- and inter-batch precision of the method were less than 8.8 and 9.8%, respectively. The intra- and inter-batch accuracies ranged from 97.5 to 104.0%. The lowest limit of quantification for FK506 was 0.5 ng/mL. The method was applied to a FK506 tissue distribution study with or without a dose of Wuzhi (WZ) tablet. Most of the FK506 tissue concentrations were slightly increased after a concomitant WZ tablet dose, but the whole blood concentration of FK506 was dramatically increased 3-fold after a concomitant WZ tablet dose. These results indicated that the LC-MS/MS method was rapid and sensitive enough to quantify FK506 in different rat tissues, and strict drug monitoring is recommended when co-administering WZ tablet in clinical use.

Purpose: To explore the potential of photoacoustictomography(PAT), as an emerging optical imaging technology, for early diagnosis of inflammatory joint disorders and accurate monitoring of disease progression and response to therapy. Methods: Pulsed laser light in the near‐infrared (NIR) region was directed toward a joint with resultant ultrasonic signals recorded and used to reconstruct images that present the optical properties in subsurface joint tissues. The feasibility of this bench‐top joint imaging system in delineating soft articular tissue structures in a noninvasive manner was validated first on rat models and then on human peripheral joints harvested from fresh cadavers. Based on the study on a commonly used adjuvant induced arthritis rat model, the capability of PAT to differentiate arthritic joints from the normal was also examined. Results: With sufficient imaging depth in the NIR region, PAT can realize tomographic imaging of a human or a small‐animal joint as a whole organ noninvasively. Based on the optical contrast, various intra‐ and extra‐articular tissues, including skin, fat, muscle, blood vessels, periosteum and bone, were presented successfully in images with satisfactory spatial resolution that was primarily limited by the bandwidth of detected photoacoustic signals rather than by optical diffusion as occurs in traditional optical imaging. In comparison with the images from the normal joints, significant differences were found in the images from the inflammatory joints, including enlarged periosteum diameter and enhanced intra‐articular optical absorption. Conclusions: By presenting additional optical contrast and tissue functional information such as blood volume and blood oxygen saturation, PAI is a natural and promising complement to conventional ultrasound technologies for musculoskeletal imaging.PAT, with its intrinsic advantages, may provide a unique opportunity to enable early diagnosis of inflammatory joint disorders, e.g. rheumatoid arthritis, and to monitor therapeutic outcomes with improved sensitivity and accuracy.

Purpose: Digital breast tomosynthesis (DBT) offers poor image quality along the depth direction. This paper presents a new method that improves the image quality of DBT considerably through the a priori information from automated ultrasound (AUS) images. Methods: DBT and AUS images of a complex breast-mimicking phantom are acquired by a DBT/AUS dual-modality system. The AUS images are taken in the same geometry as the DBT images and the gradient information of the in-slice AUS images is adopted into the new loss functional during the DBT reconstruction process. The additional data allow for new iterative equations through solving the optimization problem utilizing the gradient descent method. Both visual comparison and quantitative analysis are employed to evaluate the improvement on DBT images. Normalized line profiles of lesions are obtained to compare the edges of the DBT and AUS-corrected DBT images. Additionally, image quality metrics such as signal difference to noise ratio (SDNR) and artifact spread function (ASF) are calculated to quantify the effectiveness of the proposed method. Results: In traditional DBT image reconstructions, serious artifacts can be found along the depth direction (Z direction), resulting in the blurring of lesion edges in the off-focus planes parallel to the detector. However, by applying the proposed method, the quality of the reconstructed DBT images is greatly improved. Visually, the AUS-corrected DBT images have much clearer borders in both in-focus and off-focus planes, fewer Z direction artifacts and reduced overlapping effect compared to the conventional DBT images. Quantitatively, the corrected DBT images have better ASF, indicating a great reduction in Z direction artifacts as well as better Z resolution. The sharper line profiles along the Y direction show enhancement on the edges. Besides, noise is also reduced, evidenced by the obviously improved SDNR values. Conclusions: The proposed method provides great improvement on the quality of DBT images. This improvement makes it easier to locate and to distinguish a lesion, which may help improve the accuracy of the diagnosis using DBT imaging.

Purpose: To pave the road toward successful application of photoacoustic imaging(PAI) to breast cancer, an initial evaluation of a home fabricated PAIsystem designed deliberately to achieve high sensitivity for the detection and characterization of vascular anomalies in the breast in the mammographic geometry was completed. Method and Materials: Signal detection from deep breast was achieved by a broadband 2D PVDF planar array that has a round shape with one side trimmed straight to improve fit near the chest wall. This array has 572 active elements and a −6dB bandwidth of 0.6–1.7 MHz. The low frequency of the array enhances imaging depth and increases the size of vascular collections displayed without edge enhancement. The photoacoustic signals from all the elements go through low noise preamplifiers in the probe that are very close to the array elements for optimized noise control. Driven by 20 independent on‐probe signal processing channels, imaging with both high sensitivity and good speed was achieved. Results: According to our measurements, the end of cable sensitivity was 2.5mV/Pa. Without averaging, the minimum detectable pressure was 80 Pa. Based on the measurements of a point object at different distances from the surface of the array, the lateral resolution of the system ranges from 2.9 mm to 4.2mm and axial resolution ranges from 1.9 mm to 3.7 mm within the distance of 60 mm. To evaluate the imaging depth of this system, artificial vessels embedded deeply in ex vivo breasts harvested from fresh cadavers were imaged. Using near‐infrared laser light with incident energy density within the ANSI safety limit, imaging depth of up to 49 mm in human breasts was achieved. To validate the multi‐modality imaging possibility, PAIimages of a compressed breast containing a catheter balloon filled with blood was coregistered with ultrasoundimages acquired from the same specimen. PAI, based on the intrinsic tissue optical contrast, successfully presented some breast tissue features, including the interfaces on both sides of the skin, the connective tissue sheet in subcutaneous fat, and the lobar capsule. Conclusions: The current imaging speed of this system is adequate for laboratory research and in vivo human studies with small numbers of cooperative volunteers. With a high power tunable laser working on multiple wavelengths, this system might contribute to 3D noninvasive imaging of morphological and physiological tissue features throughout the breast.

Purpose: To add spectroscopicphotoacoustictomography (S‐PAT) to an ultrasound imagingsystem in the mammographic geometry to test whether this minimally invasive and ultimately inexpensive modality can detect and interpret small vascular anomalies, providing information supplemental to that of x‐ray and ultrasound much as is done with MRI. Blood oxygenation and blood volume information from S‐PAT might replace or exceed information provided by MRI resolution, possibly without contrast agents. Method and Materials: The specimen surface is flooded with a