Olivier Couture

We present an open-source code for 3D super-resolution ultrasound imaging. Open-3DULM was applied to transcranial imaging in habituated awake mice. Comparative analysis reveals that isoflurane anesthesia induces significant vasodilation and increased cerebral blood flow (CBF) in veins, while only a subset of arteries exhibits these effects compared to the awake state. This method could serve as a reference for developing new types of 3D vascular quantifications, particularly emphasizing the importance of awake and 3D imaging for accurate cerebral blood flow measurement in neuroscience research.

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition with high rates of secondary complications such as delayed cerebral ischemia (DCI). Early detection of perfusion deficits is critical but remains challenging with conventional imaging modalities that are intermittent, non-portable, and provide limited temporal resolution. Here, we evaluate a novel investigational platform for volumetric acoustic angiography and bedside cerebral perfusion imaging using three-dimensional contrast-enhanced ultrasound (3D CEUS). In a prospective feasibility study, eleven aSAH patients underwent bilateral 3D CEUS at admission, day 5, and day 10 in the neurocritical care unit. The system enabled reconstruction of 3D microvascular volumes and time-intensity evolution (TIE) curves for cerebral blood flow (CBF) assessment. Global perfusion measurements were successful in 95% of acquisitions. Notably, TIE-derived perfusion patterns at day 5 showed strong correlation with poor neurological outcome (88.9% accuracy) suggesting the prognostic potential of the technique. This study demonstrates, for the first time, the feasibility of bedside volumetric CEUS for dynamic assessment of cerebral perfusion in patients with aSAH. The method offers high spatial and temporal resolution, real-time feedback, and correlation with clinical trajectory. These findings position three dimensional CEUS-based acoustic angiography as a promising tool for early detection of DCI and improved neuromonitoring in the intensive care unit.

Background: Deep brain structures are supplied by perforating arteries, which are too thin to be observed with non-invasive and widely available clinical imaging methods. In moyamoya disease, main arteries in the base of the brain progressively narrow, and perforating arteries grow densely and tortuously to compensate the lack of blood supply in deep brain structures.

We present an open-source code for 3D super-resolution ultrasound imaging. Open-3DULM was applied to transcranial imaging in habituated awake mice. Comparative analysis reveals that isoflurane anesthesia induces significant vasodilation and higher cerebral blood flow compared to the awake state. This method could serve as a reference for developing new types of 3D vascular quantifications, particularly emphasizing the importance of awake and 3D imaging for accurate cerebral blood flow measurement in neuroscience research.

Super-resolution ultrasound (SRUS) has evolved significantly with the advent of Ultrasound Localization Microscopy (ULM). This technique enables sub-wavelength resolution imaging using microbubble contrast agents. Initially confined to 2D imaging, ULM has progressed towards volumetric approaches, allowing for comprehensive three-dimensional visualization of microvascular networks. This review explores the technological advancements and challenges associated with volumetric ULM, focusing on key aspects such as transducer design, acquisition speed, data processing algorithms, or integration into clinical practice. We discuss the limitations of traditional 2D ULM, including dependency on precise imaging plane selection and compromised resolution in microvasculature quantification. In contrast, volumetric ULM offers enhanced spatial resolution and allowed motion correction in all direction, promising transformative insights into microvascular pathophysiology. By examining current research and future directions, this review highlights the potential of volumetric ULM to contribute significantly to diagnostic across various medical conditions, including cancers, arteriosclerosis, strokes, diabetes, and neurodegenerative diseases.

We present an open-source code for 3D super-resolution ultrasound imaging. Open-3DULM was applied to transcranial imaging in habituated awake mice. Comparative analysis reveals that isoflurane anesthesia induces significant vasodilation and higher cerebral blood flow compared to the awake state. This method could serve as a reference for developing new types of 3D vascular quantifications, particularly emphasizing the importance of awake and 3D imaging for accurate cerebral blood flow measurement in neuroscience research.

Background Deep brain structures are supplied by perforating arteries, these arteries are too thin to be observed with non-invasive and widely available clinical imaging methods. In Moya Moya disease, main arteries in the base of the brain progressively narrowed, and perforating arteries grow densely and tortuously to compensate the lack of blood supply in deep brain structures. Purpose The aim of this study is to evaluate the efficacy of transcranial ultrasound localization microscopy (ULM) in visualizing perforating arteries, utilizing a standard low-frame-rate ultrasound clinical scanner and contrast sequences commonly employed in hospital settings. Methods This prospective single-center study included ischemic stroke patients not related to perforating arteries, i.e. control patients, and Moya Moya disease patients (n° 2022-A02486-37). Contrast-enhanced ultrasound sequences (CEUS) were performed by an experienced neurologist and the images acquired were used to perform post-processing ULM. ULM density maps, i.e. number of microbubbles tracked per pixel, were compared with conventional 3T TOF MRI and color Doppler imaging (one-way ANOVA test). We also compared ULM density maps between the control and Moya Moya groups (two-sided parametric Student’s t-tests, or Mann-Whitney test). Results We included a group of 15 control patients and another group of 9 Moya Moya patients between March 2023 and March 2024. The patients had an average age of 45 years with 65% of them being male. Perforating arteries were captured on all subjects, with a mean diameter of 0.8 ± 0.3 mm in control patients, while it was not so far possible with TOF MRI or color Doppler (P < 0.05). Moreover, ULM enabled the differentiation between healthy subjects and those with Moya Moya disease through track mean distance (P = 0.05). Conclusions Using a low-frame-rate ultrasound scanner, CEUS and accessible post-processing tools, we have demonstrated that transcranial ULM can facilitate the visualization and characterization of perforating arteries, even in cases where they were previously undetectable using standard non-invasive imaging techniques. We speculate that with the advent of high-frame-rate 3D ULM, this technique may find widespread utility in hospitals. Key Results - 2D low-frame rate Ultrasound Localization Microscopy (ULM) allows visualization of perforating arteries, i.e. diameter of 0.8 ± 0.3 mm. - ULM described vessels that were not visible in conventional imaging techniques, i.e. TOF MRI and color Doppler. - ULM reconstruction and quantification of the perforating arteries enabled the pathological group (Moya Moya) to be distinguished from control subjects. Summary statement Transcranial 2D ULM performed with a standard low frame-rate clinical ultrasound scanner enabled visualization and morphological description of perforating arteries. The study involved 24 subjects, including 9 Moya Moya patients.

Ultrasound Localization Microscopy (ULM) has been applied in various preclinical settings and in the clinic to reveal the microvasculature in deep organs. However, most ULM images employ standard Delay-and-Sum (DAS) beamforming. In standard ULM conditions, lengthy acquisition times are required to fully reconstruct small vessels due to the need for spatially isolated microbubbles, resulting in low temporal resolution. When microbubbles are densely packed, localizing a point spread function with significant main and side lobes becomes challenging due to matrix arrays’ low signal-to-noise ratio and spatial resolution. In this work, we applied adaptive beamforming such as high order DAS known as (pDAS), Coherence Factor (CF), Coherence Factor with Gaussian Filtering (CFGF), and statistical interpretation of beamforming (iMAP) to provide a more complete 3D ULM maps in vitro and in vivo (rat kidney). Specifically, the CF and 1MAP adaptive beamformers achieved higher resolution (32.9 microns and 27.2 microns respectively), as measured by the Fourier Shell Correlation (FSC), compared to the standard DAS beamformer, which had an FSC value of 38.6 microns.

Cerebral circulation ensures the proper functioning of the entire human body, and its interruption, i.e. stroke, leads to irreversible damage. However, tools for observing cerebral circulation are still lacking. Although MRI and CT scans serve as conventional methods, their accessibility remains a challenge, prompting exploration into alternative, portable, and non-ionizing imaging solutions like ultrasound with reduced costs. While Ultrasound Localization Microscopy (ULM) displays potential in high-resolution vessel imaging, its 2D constraints limit its emergency utility. This study delves into the feasibility of 3D ULM with multiplexed probe for transcranial vessel imaging in sheep brains, emulating human skull characteristics. Three sheep underwent 3D ULM imaging, compared with angiographic MRI, while skull characterization was conducted in vivo using ultrashort bone MRI sequences and ex vivo via micro CT. The study showcased 3D ULM’s ability to highlight vessels, down to the Circle of Willis, yet within a confined 3D field-of-view. Future enhancements in signal, aberration correction, and human trials hold promise for a portable, volumetric, transcranial ultrasound angiography system.