Tracking of biodynamics across entire living organisms is essential for understanding complex biology and disease progression. The presently available small‐animal functional and molecular imaging ...modalities remain constrained by factors including long image acquisition times, low spatial resolution, limited penetration or poor contrast. Here flash scanning volumetric optoacoustic tomography (fSVOT), a new approach for high‐speed imaging of fast kinetics and biodistribution of optical contrast agents in whole mice that simultaneously provides reference images of vascular and organ anatomy with unrivaled fidelity and contrast, is presented. The imaging protocol employs continuous overfly scanning of a spherical matrix array transducer, accomplishing a 200 µm resolution 3D scan of the whole mouse body within 45 s without relying on signal averaging. This corresponds to an imaging speed gain of more than an order of magnitude compared with existing state‐of‐the‐art implementations of comparable resolution performance. Volumetric tracking and quantification of gold nanoagent and near infrared (NIR)‐II dye kinetics and their differential uptake in various organs are demonstrated. fSVOT thus offers unprecedented capabilities for multiscale imaging of pharmacokinetics and biodistribution with high contrast, resolution, and speed.
Herein, flash scanning volumetric optoacoustic tomography (fSVOT), a new approach for high‐speed imaging of fast kinetics and biodistribution of optical contrast agents in the second near infrared (NIR‐II) window in entire mice, is introduced. The method effectively reduces high‐resolution total‐body image acquisition times to sub‐minute levels, taking whole‐body small animal molecular imaging to a new level of spatiotemporal resolution performance.
In article number 2000484, Avihai Ron, Sandeep Kalva, and co‐workers introduce a new biomedical imaging approach termed flash‐scanning volumetric optoacoustic tomography (fSVOT). The method offers ...unprecedented abilities for preclinical whole‐body anatomical, functional, and molecular imaging with superb contrast, resolution, and speed, further enabling time‐lapse fully multiplexed observations of contrast agent perfusion and accumulation across multiple organs.
Purpose
Diabetes is associated with a deterioration of the microvasculature in brown adipose tissue (BAT) and with a decrease in its metabolic activity. Multispectral optoacoustic tomography has been ...recently proposed as a new tool capable of differentiating healthy and diabetic BAT by observing hemoglobin gradients and microvasculature density in cross-sectional (2D) views. We report on the use of spiral volumetric optoacoustic tomography (SVOT) for an improved characterization of BAT.
Procedures
A streptozotocin-induced diabetes model and control mice were scanned with SVOT. Volumetric oxygen saturation (sO
2
) as well as total blood volume (TBV) in the subcutaneous interscapular BAT (iBAT) was quantified. Segmentation further enabled separating feeding and draining vessels from the BAT anatomical structure.
Results
Scanning revealed a 46 % decrease in TBV and a 25 % decrease in sO
2
in the diabetic iBAT with respect to the healthy control.
Conclusions
These results suggest that SVOT may serve as an effective tool for studying the effects of diabetes on BAT. The volumetric optoacoustic imaging probe used for the SVOT scans can be operated in a handheld mode, thus potentially providing a clinical translation route for BAT-related studies with this imaging technology.
Respiratory motion in living organisms is known to result in image blurring and loss of resolution, chiefly due to the lengthy acquisition times of the corresponding image acquisition methods. ...Optoacoustic tomography can effectively eliminate in vivo motion artifacts due to its inherent capacity for collecting image data from the entire imaged region following a single nanoseconds-duration laser pulse. However, multi-frame image analysis is often essential in applications relying on spectroscopic data acquisition or for scanning-based systems. Thereby, efficient methods to correct for image distortions due to motion are imperative. Herein, we demonstrate that efficient motion rejection in optoacoustic tomography can readily be accomplished by frame clustering during image acquisition, thus averting excessive data acquisition and post-processing. The algorithm’s efficiency for two- and three-dimensional imaging was validated with experimental whole-body mouse data acquired by spiral volumetric optoacoustic tomography (SVOT) and full-ring cross-sectional imaging scanners.
Machine learning (ML) has become an essential asset for the life sciences and medicine. We selected 250 articles describing ML applications from 17 journals sampling 26 different fields between 2011 ...and 2016. Independent evaluation by two readers highlighted three results. First, only half of the articles shared software, 64% shared data and 81% applied any kind of evaluation. Although crucial for ensuring the validity of ML applications, these aspects were met more by publications in lower-ranked journals. Second, the authors’ scientific backgrounds highly influenced how technical aspects were addressed: reproducibility and computational evaluation methods were more prominent with computational co-authors; experimental proofs more with experimentalists. Third, 73% of the ML applications resulted from interdisciplinary collaborations comprising authors from at least two of the three disciplines: computational sciences, biology, and medicine. The results suggested collaborations between computational and experimental scientists to generate more scientifically sound and impactful work integrating knowledge from both domains. Although scientifically more valid solutions and collaborations involving diverse expertise did not correlate with impact factors, such collaborations provide opportunities to both sides: computational scientists are given access to novel and challenging real-world biological data, increasing the scientific impact of their research, and experimentalists benefit from more in-depth computational analyses improving the technical correctness of work.Applications of machine learning in the life sciences and medicine require expertise in computational methods and in scientific subject matter. The authors surveyed articles in the life sciences that included machine learning applications, and found that interdisciplinary collaborations increased the scientific validity of published research.
Doxorubicin (DOX) is a widely used chemotherapeutic anticancer drug. Its intrinsic fluorescence properties enable investigation of tumor response, drug distribution and metabolism. First phantom ...studies in vitro showed optoacoustic property of DOX. We therefore aimed to further investigate the optoacoustic properties of DOX in biological tissue in order to explore its potential as theranostic agent. We analysed doxorubicin hydrochloride (Dox·HCl) and liposomal encapsulated doxorubicin hydrochloride (Dox·Lipo), two common drugs for anti-cancer treatment in clinical medicine. Optoacoustic measurements revealed a strong signal of both doxorubicin substrates at 488 nm excitation wavelength. Post mortem analysis of intra-tumoral injections of DOX revealed a detectable optoacoustic signal even at three days after the injection. We thereby demonstrate the general feasibility of doxorubicin detection in biological tissue by means of optoacoustic tomography, which could be applied for high resolution imaging at mesoscopic depths dictated by effective penetration of visible light into the biological tissues.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mapping tumor heterogeneity and hypoxia within a living intact organism is essential for understanding the processes involved in cancer progression and assessing long-term responses to therapies. ...Efficient investigations into tumor hypoxia mechanisms have been hindered by the lack of intravital imaging tools capable of multiparametric probing of entire solid tumors with high spatial and temporal resolution. Here, we exploit volumetric multispectral optoacoustic tomography (vMSOT) for accurate, label-free delineation of tumor heterogeneity and dynamic oxygenation behavior. Mice bearing orthotopic MDA-MB-231 breast cancer xenografts were imaged noninvasively during rest and oxygen stress challenge, attaining time-lapse three-dimensional oxygenation maps across entire tumors with 100 μm spatial resolution. Volumetric quantification of the hypoxic fraction rendered values of 3.9% to 21.2%, whereas the oxygen saturation (sO
) rate declined at 1.7% to 2.3% per mm in all tumors when approaching their core. Three distinct functional areas (the rim, hypoxic, and normoxic cores) were clearly discernible based on spatial sO
profiles and responses to oxygen challenge. Notably, although sO
readings were responsive to the challenge, deoxyhemoglobin (HbR) trends exhibited little to no variations in all mice. Dynamic analysis further revealed the presence of cyclic hypoxia patterns with a 21% average discrepancy between cyclic fractions assessed via sO
(42.2% ± 17.3%) and HbR fluctuations (63% ± 14.1%) within the hypoxic core. These findings corroborate the strong potential of vMSOT for advancing preclinical imaging of cancer and informing clinical decisions on therapeutic interventions.
vMSOT provides quantitative measures of volumetric hypoxic fraction and cyclic hypoxia in a label-free and noninvasive manner, providing new readouts to aid tumor staging and treatment decision making.
http://cancerres.aacrjournals.org/content/canres/00/0/000/F1.large.jpg.
Goal. The purpose of this computer modeling study is to validate the feasibility of a home monitoring system for wrist bone mineral density (BMD) measurement which is based on the parametric ...electrical impedance tomography (pEIT) method. Methods. A solution to the forward problem of the developing potential around the wrist due to current injection was developed using a Matlab numerical simulation of an adult computer human phantom. The backward problem is solved by building a lookup table of different bone densities which represent different disease stages. Results. The real part of the complex potential exhibits an average change of 30.7%-12% (between the most sensitive and the least sensitive electrodes) per BMD decrease of 23%. A 2 times higher sensitivity to a deterioration of the cortical bone than of the trabecular bone alone was found. A signal to noise ratio (SNR) level above 30 dB is required for a maximal performance of the system. The robustness to a deposition of the electrodes array in different directions is limited. Conclusion. It was found that the cortical BMD changes govern the model. The required SNR level is within the specs of similar systems. In a real device, the issue of sensors repositioning should be addressed. The proposed pEIT system makes self-monitoring of wrist BMD possible. It brings an added-value by enabling the monitoring of BMD between treatments and between traditional DEXA screenings.
Exposure to the microgravity environment results in various adaptive and maladaptive physiological changes in the human body, with notable ophthalmic abnormalities developing during 6-mo missions on ...the International Space Station (ISS). These findings have led to the hypothesis that the loss of gravity induces a cephalad fluid shift, decreased cerebral venous outflow, and increased intracranial pressure, which may be further exacerbated by increased ambient carbon dioxide (CO
) levels on the ISS. Here we describe the SPACECOT study (studying the physiological and anatomical cerebral effects of CO
during head-down tilt), a randomized, double-blind crossover design study with two conditions: 29 h of 12° head-down tilt (HDT) with ambient air and 29 h of 12° HDT with 0.5% CO
The internationally collaborative SPACECOT study utilized an innovative approach to study the effects of headward fluid shifting induced by 12° HDT and increased ambient CO
as well as their interaction with a focus on cerebral and ocular anatomy and physiology. Here we provide an in-depth overview of this new approach including the subjects, study design, and implementation, as well as the standardization plan for nutritional intake, environmental parameters, and bed rest procedures.
A new approach for investigating the combined effects of cephalad fluid shifting and increased ambient carbon dioxide (CO
) is presented. This may be useful for studying the neuroophthalmic and cerebral effects of spaceflight where cephalad fluid shifts occur in an elevated CO
environment.
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