S100A8/A9: From basic science to clinical application.

Biomarkers for monitoring of disease progression and response to therapy are lacking for muscle diseases such as Duchenne muscular dystrophy. Noninvasive in vivo molecular imaging with multispectral optoacoustic tomography (MSOT) uses pulsed laser light to induce acoustic pressure waves, enabling the visualization of endogenous chromophores. Here we describe an application of MSOT, in which illumination in the near- and extended near-infrared ranges from 680–1,100 nm enables the visualization and quantification of collagen content. We first demonstrated the feasibility of this approach to noninvasive quantification of tissue fibrosis in longitudinal studies in a large-animal Duchenne muscular dystrophy model in pigs, and then applied this approach to pediatric patients. MSOT-derived collagen content measurements in skeletal muscle were highly correlated to the functional status of the patients and provided additional information on molecular features as compared to magnetic resonance imaging. This study highlights the potential of MSOT imaging as a noninvasive, age-independent biomarker for the implementation and monitoring of newly developed therapies in muscular diseases. Imaging of muscle fibrosis with a handheld device could potentially serve as a biomarker for disease progression and response to therapy in patients with Duchenne muscular dystrophy.

/pdf/detection-of-collagens-by-multispectral-optoacoustic-5f9oygso7i.pdf

Detection of collagens by multispectral optoacoustic tomography as an imaging biomarker for Duchenne muscular dystrophy.

For decades now, photoacoustic imaging (PAI) has been investigated to realize its potential as a niche biomedical imaging modality. Despite its highly desirable optical contrast and ultrasonic spatiotemporal resolution, PAI is challenged by such physical limitations as a low signal-to-noise ratio (SNR), diminished image contrast due to strong optical attenuation, and a lower-bound on spatial resolution in deep tissue. In addition, contrast-enhanced PAI has faced practical limitations such as insufficient cell-specific targeting due to low delivery efficiency and difficulties in developing clinically translatable agents. Identifying these limitations is essential to the continuing expansion of the field, and substantial advances in developing contrast-enhancing agents, complemented by high-performance image acquisition systems, have synergistically dealt with the challenges of conventional PAI. This review covers the past four years of research on pushing the physical and practical challenges of PAI in terms of SNR/contrast, spatial resolution, targeted delivery, and clinical application. Promising strategies for dealing with each challenge are reviewed in detail, and future research directions for next generation contrast-enhanced PAI are discussed.

Recent Advances in Contrast-Enhanced Photoacoustic Imaging: Overcoming the Physical and Practical Challenges.

Multispectral optoacoustic tomography (MSOT) represents a new in vivo imaging technique with high resolution (~250 μm) and tissue penetration (>1 cm) using the photoacoustic effect. While ultrasound contains anatomical information for lesion detection, MSOT provides functional information based on intrinsic tissue chromophores. We aimed to evaluate the feasibility of combined ultrasound/MSOT imaging of breast cancer in patients compared to healthy volunteers. Imaging was performed using a handheld MSOT system for clinical use in healthy volunteers (n = 6) and representative patients with histologically confirmed invasive breast carcinoma (n = 5) and ductal carcinoma in situ (DCIS, n = 2). MSOT values for haemoglobin and oxygen saturation were assessed at 0.5, 1.0 and 1.5 cm depth and selected wavelengths between 700 and 850 nm. Reproducible signals were obtained in all wavelengths with consistent MSOT signals in superficial tissue in breasts of healthy individuals. In contrast, we found increased signals for haemoglobin in invasive carcinoma, suggesting a higher perfusion of the tumour and tumour environment. For DCIS, MSOT values showed only little variation compared to healthy tissue. This preliminary MSOT breast imaging study provided stable, reproducible data on tissue composition and physiological properties, potentially enabling differentiation of solid malignant and healthy tissue. • A handheld MSOT probe enables real-time molecular imaging of the breast.
 • MSOT of healthy controls provides a reproducible reference for pathology identification.
 • MSOT parameters allows for differentiation of invasive carcinoma and healthy tissue.

Multispectral optoacoustic tomography of the human breast: characterisation of healthy tissue and malignant lesions using a hybrid ultrasound-optoacoustic approach.

Monocytes and macrophages are central players of the innate immune response and play a pivotal role in the regulation of inflammation. Thereby, they actively participate in all phases of the immune response, from initiating inflammation and triggering the adaptive immune response, through to the clearance of cell debris and resolution of inflammation. In this review, we described the mechanisms of monocyte and macrophage adaptation to rapidly changing microenvironmental conditions and discussed different forms of macrophage polarization depending on the environmental cues or pathophysiological condition. Therefore, special focus was placed on the tight regulation of the pro- and anti-inflammatory immune response, and the diverse functions of S100A8/S100A9 proteins and the scavenger receptor CD163 were highlighted, respectively. We paid special attention to the function of pro- and anti-inflammatory macrophages under pathological conditions.

https://www.mdpi.com/2073-4409/11/12/1979/pdf?version=1655780582

The Good and the Bad: Monocytes’ and Macrophages’ Diverse Functions in Inflammation

Background
MR headphones are attenuation sources affecting PET quantification in hybrid PET/MRI. Despite potentially better patient communication, usage in PET/MRI scans is not approved by the vendor. This study aims to determine the impact of headphones on PET by means of phantom and patient scans. Additionally, the perceived benefit of using headphones was evaluated.

/pdf/impact-of-mr-safe-headphones-on-pet-attenuation-in-combined-k5zhjr4bi4.pdf

Impact of MR-safe headphones on PET attenuation in combined PET/MRI scans

450 Objectives To assess the overall, intra-patient and inter-patient heterogeneity of SUVmax in metastatic renal cell cancer (mRCC) and metastatic lung cancer (mLC), using variance as a measure of heterogeneity. Methods Twenty-two patients with mRCC and 16 patients with mLC and a pre-therapy FDG PET/CT were included in this retrospective study. SUVmax in metastatic lesions larger than 1.5 cm was calculated by placing a 3-D ROI. The total variance of SUVmax in each patient group was estimated using variance-components models. The intra-patient and inter- patient components of the total variance in each patient group were estimated using the method of maximum-likelihood and compared, using a Wald test (on the scale of log ratios). Results There were 76 metastatic lesions in 22 mRCC patients (2-6 lesions per patient) and 82 metastatic lesions in 16 mLC patients (2-16 lesions per patient). SUVmax ranged from 1.9 to 21.3 (mean + SD: 6.7 + 4.2) in mRCC and from 4.7 to 65.9 (mean + SD: 14.5 + 8.6) in mLC (P Conclusions The total heterogeneity of SUVmax is higher in mLC than in mRCC. In both groups, the much larger component of the heterogeneity is inter-patient, and 4-fold (mRCC) to 6-fold (mLC) larger than the intra-patient component of the heterogeneity. These results support the existence of a disease and patient-specific metabolic signature. At the same time, the relatively little intra-patient heterogeneity may indicate that any metastatic lesion in a patient could be used as the index lesion for follow-up after therapy. These preliminary results need to be confirmed in larger groups of patients and other malignancies.

https://jnm.snmjournals.org/content/jnumed/56/3/450.full.pdf

Optical in vivo imaging of the alarmin S100A9 in tumor lesions allows for estimation of the individual malignant potential by evaluation of tumor-host cell interaction.

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Multispectral optoacoustic tomography of the human breast: characterisation of healthy tissue and malignant lesions using a hybrid ultrasound-optoacoustic approach.

Impact of MR-safe headphones on PET attenuation in combined PET/MRI scans

Optical in vivo imaging of the alarmin S100A9 in tumor lesions allows for estimation of the individual malignant potential by evaluation of tumor-host cell interaction.