Photoacoustic (PA) imaging is a functional and molecular imaging technique capable of high sensitivity and spatiotemporal resolution at depth. Widespread use of PA imaging, however, is limited by currently available contrast agents, which either lack PA-signal-generation ability for deep imaging or their absorbance spectra overlap with hemoglobin, reducing sensitivity. Here we report on a PA contrast agent based on targeted liposomes loaded with J-aggregated indocyanine green (ICG) dye (i.e., PAtrace) that we synthesized, bioconjugated, and characterized to addresses these limitations. We then validated PAtrace in phantom, in vitro, and in vivo PA imaging environments for both spectral unmixing accuracy and targeting efficacy in a folate receptor alpha-positive ovarian cancer model. These study results show that PAtrace concurrently provides significantly improved contrast-agent quantification/sensitivity and SO2 estimation accuracy compared to monomeric ICG. PAtrace’s performance attributes and composition of FDA-approved components make it a promising agent for future clinical molecular PA imaging.

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Exposure to endocrine-disrupting chemicals (EDCs) has been suggested to contribute to the increasing trends of external genital malformation in male newborns. In Northeastern Brazil, the poor sanitary conditions found in the favelas encourage the widespread use of pesticides. This 2-year study of a total birth cohort of full-term male newborns in the regional hospitals of Campina Grande (Paraíba, Brazil) sought to (1) accurately establish for the first time the incidences of neonatal male genital malformations, (2) investigate the endocrine and genetic aetiologies of these malformations, and (3) evaluate their associations with possible prenatal exposure to EDCs. A total of 2710 male newborns were explored for cryptorchidism, hypospadias and micropenis. Cases were referred to the Pediatric Endocrine Clinic for endocrine and genetic investigations, and all parents were interviewed about their environmental/occupational exposure to EDCs before/during pregnancy by paediatric endocrinologists using a detailed questionnaire. We observed 56 cases of genital malformation (2.07%), including 23 cryptorchidism (0.85%), 15 hypospadias (0.55%), and 18 micropenis (0.66%). All cases exhibited normal/subnormal testosterone production and none presented androgen receptor or 5α-reductase gene mutation. More than 92% of these newborns presented foetal contamination by EDCs, as their mothers reported daily domestic use of pesticides (i.e., DDT) and other EDCs. Most of these undervirilized male newborns presented additional EDC contamination, as 80.36% of the mothers and 58.63% of the fathers reported paid or unpaid work that entailed the use of pesticides and other EDCs before/during pregnancy for the mothers and around the time of fertilization for the fathers. The high rate of micropenis in our population associated with an elevated percentage of parental environmental/occupational exposure to EDCs before/during pregnancy indicates that foetal contamination may be a risk factor for the development of male external genital malformation.

Several methods have been developed over the last several years to analyze the mechanical properties of soft tissue. Elastography, for example, was proposed to evaluate soft tissue stiffness in an attempt to reduce the need for invasive procedures, such as breast biopsies; however, its qualitative nature and the fact that it is operator-dependent have proven to be limitations of the technique. Quantitative shearwave- based techniques have been proposed to obtain information about tissue stiffness independent of the operator. This paper describes shear wave dispersion magnetomotive ultrasound (SDMMUS), a new shear-wave-based method in which a viscoelastic medium labeled with iron oxide nanoparticles is displaced by an external tone burst magnetic field. As in magnetomotive ultrasound (MMUS), SDMMUS uses ultrasound to detect internal mechanical vibrations induced by the interaction between a magnetic field and magnetic nanoparticles. These vibrations generated shear waves that were evaluated to estimate the viscoelastic properties of tissue-mimicking phantoms. These phantoms were manufactured with different concentrations of gelatin and labeled with iron oxide nanoparticles. The elasticity and viscosity obtained with SDMMUS agreed well with the results obtained by traditional ultrasound-based transient elastography.

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A variety of hematological diseases manifest in the bone marrow (BM), broadly characterized as BM failure (BMF). BMF can be caused by acute lymphoblastic leukemia (ALL), which results in an expansion of hypoxic regions in the BM. Because of this hypoxic presentation, there is potential for improved characterization of BMF through in vivo assessment of oxygenation in the BM cavity. Photoacoustic (PA) imaging can provide local assessment of intravascular oxygen saturation (SO 2 ), which has been shown to correlate with pimonidazole-assessed hypoxia. This study introduces an optimized PA imaging technique to assess SO 2 within the femoral BM cavity through disease progression in a murine model of ALL. Results show a statistically significant difference with temporal changes in SO 2 (from baseline) between control and diseased cohorts, demonstrating the potential of PA imaging for noninvasive, label-free monitoring of BMF diseases.

As photoacoustic (PA) imaging makes its way into the clinic, the accuracy of PA-based metrics becomes increasingly important. To address this need, a method combining finite-element-based local fluence correction (LFC) with signal-to-noise-ratio (SNR) regularization was developed and validated to accurately estimate oxygen saturation (SO 2 ) in tissue. With data from a Vevo LAZR system, performance of our LFC approach was assessed in ex vivo blood targets (37.6%-99.6% SO 2 ) and in vivo rat arteries. Estimation error of absolute SO 2 and change in SO 2 reduced from 10.1% and 6.4%, respectively, without LFC to 2.8% and 2.0%, respectively, with LFC, while the accuracy of the LFC method was correlated with the number of wavelengths acquired. This paper demonstrates the need for an SNRregularized LFC to accurately quantify SO 2 with PA imaging.

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