Design And Development Of A Miniaturized Combined Ultrasound /photoacoustic Endoscopic System

Gynecological cancer is the fourth most common cancer among women in the worldwide. As is the case for most kinds of cancers, early detection can increase the chances of treatment success. One of the significant challenges in diagnosing patients with cervical cancer involves detecting tumor extension within the cervical canal. Currently, conization or cone biopsy is a clinical procedure that involves the surgical resection of the cone-shaped volume of the high-grade dysplastic or cancerous cervical tissue size of the resected tissue. However, there are risks associated with this procedure, including primary or secondary hemorrhage, cervical stenosis, and subsequent infertility or an abnormal pregnancy. Thus, there is currently an unmet clinical need for developing an imaging system capable of providing accurate structural, functional, and molecular data for the early-stage detection of clinical biomarkers in cervical cancers. This Ph.D. dissertation introduces a miniaturized phased-array ultrasound (US) and photoacoustic (PA) theranostic system capable of providing multi-modal diagnostic information of gynecologic diseases such as cervical cancer. Additionally, it is capable of simultaneous tissue ablation. The developed PA/US endoscope consists of two parts: (1). an integrated endoscopic system that consists of a phased-array ultrasound endoscope, a compact light delivery system, and a sheath for imaging through the cervical canal, and (2) an external illumination system for delivering light to cervix tissue through the ectocervix. The integrated internal US/PA system consists of a 64-element phased-array US probe for providing a high-resolution 90-degrees sector imaging and seven silica core optical fibers (550 µm core diameter) for our internal light delivery system. The US probe is surrounded by these fibers, which project the laser light and ablation beam toward the tissue in front of the active aperture and yield aligned and overlapped US waves and light beams. In addition, a custom-built housing is designed to integrate light delivery and US imaging into a portable and compact system for cross-patient imaging. The total size of the internal theranostic system measures 6.89 mm, which allows it to access the cervical tissue in close proximity when positioned through the cervical canal. The external illumination is comprised of seven optical fibers polished and encapsulated inside a borosilicate capillary tube. Several simulations and ex vivo phantom studies have been conducted to characterize and evaluate the performance of the endoscope. Preliminary ex vivo phantom and tissue studies have shown high resolution and high contrast PA images. Additional ex-vivo studies have verified the tissue distinguishing capability of the theranostic endoscope by analyzing the measurable differences in the PA signal between pre-and post-ablated tissue. The results of an increase in the PA signal with temperature variations confirmed the ability of the proposed endoscope to provide real-time temperature feedback

Integrated Ultrasound and Photoacoustic-Guided Laser Ablation Theranostic Endoscopic System

Advancements in ablation techniques have paved the way towards the development of safer and more effective clinical procedures for treating various maladies such as atrial fibrillation (AF). AF is characterized by rapid, chaotic atrial activation and is commonly treated using radiofrequency applicators or laser ablation catheters. However, the lack of thermal lesion formation and temperature monitoring capabilities in these devices prevents them from measuring the treatment outcome directly. In addition, poor differentiation between healthy and ablated tissues leads to incomplete ablation, which reduces safety and causes complications in patients. Hence, a novel photoacoustic (PA)-guided laser ablation theranostic device was developed around a traditional phased-array endoscope. The proposed technology provides lesion formation, tissue distinguishing, and temperature monitoring capabilities. Our results have validated the lesion monitoring capability of the proposed technology through PA correlation maps. The tissue distinguishing capability of the theranostic device was verified by the measurable differences in the PA signal between pre-and post-ablated mice myocardial tissue. The increase in the PA signal with temperature variations caused by the ablation laser confirmed the ability of the proposed device to provide temperature feedback

Validation of delay-multiply-and-standard-deviation weighting factor for improved photoacoustic imaging of sentinel lymph node

Delay-and-sum (DAS) is one of the most common algorithms used to construct the photoacoustic images due to its low complexity. However, it results in images with high sidelobes and low resolution. Delay-and-standard-deviation (DASD) weighting factor can improve the contrast of the images compared to DAS. However, it still suffers from high sidelobes. In this work, a new weighting factor, named delay-multiply-and-standard-deviation (DMASD) is introduced to enhance the contrast of the reconstructed images compared to other mentioned methods. In the proposed method, the standard deviation of the mutual multiplied delayed signals are calculated, normalized and multiplied to DAS beamformed data. The results show that DMASD improves the signal-to-noise-ratio about 19.29 dB and 7.3 dB compared to DAS and DASD, respectively, for in vivo imaging of the sentinel lymph node. Moreover, the contrast-ratio is improve by the DMASD about 23.61 dB and 10.81 dB compared to DAS and DASD, respectively.Accepted versio

Regularized Capon Beamformer Using ℓ1-Norm Applied to Photoacoustic Imaging

Delay-and-Sum (DAS), as a non-adaptive beamforming method, is one of the most common algorithms used in Photoacoustic imaging due to its simple implementation. The results obtained from this algorithm suffer from low resolution and high sidelobes. The adaptive Minimum variance (MV) method improves the image quality compared to DAS in terms of resolution and contrast. In this paper, it is proposed to add a ℓ1-norm regularization term to the conventional MV minimization problem and create a new sparse beamforming method, named Modified-Sparse-Mv (ms-Mv)algorithm. In fact, the sparsity of the output is forced to the beampattern by adding this new sparse added term, which results in more noise reduction and sidelobe suppression compared to MV. The minimization problem is convex, and therefore, it can be solved using an iterative algorithm. The results show that the proposed MS-MV method improves the signal-to-noise-ratio for about 5.36 dB and 6.44 dB compared to DAS and MV, respectively, for the designed wire phantom.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.ImPhys/Acoustical Wavefield Imagin

Photoacoustic-MR Image Registration Based on a Co-Sparse Analysis Model to Compensate for Brain Shift

Brain shift is an important obstacle to the application of image guidance during neurosurgical interventions. There has been a growing interest in intra-operative imaging to update the image-guided surgery systems. However, due to the innate limitations of the current imaging modalities, accurate brain shift compensation continues to be a challenging task. In this study, the application of intra-operative photoacoustic imaging and registration of the intra-operative photoacoustic with pre-operative MR images are proposed to compensate for brain deformation. Finding a satisfactory registration method is challenging due to the unpredictable nature of brain deformation. In this study, the co-sparse analysis model is proposed for photoacoustic-MR image registration, which can capture the interdependency of the two modalities. The proposed algorithm works based on the minimization of mapping transform via a pair of analysis operators that are learned by the alternating direction method of multipliers. The method was evaluated using an experimental phantom and ex vivo data obtained from a mouse brain. The results of the phantom data show about 63% improvement in target registration error in comparison with the commonly used normalized mutual information method. The results proved that intra-operative photoacoustic images could become a promising tool when the brain shift invalidates pre-operative MRI

Spectroscopic photoacoustic imaging of cervical tissue composition in excised human samples.

ObjectiveCervical remodeling is an important component in determining the pathway of parturition; therefore, assessing changes in cervical tissue composition may provide information about the cervix's status beyond the measurement of cervical length. Photoacoustic imaging is a non-invasive ultrasound-based technology that captures acoustic signals emitted by tissue components in response to laser pulses. This optical information allows for the determination of the collagen-to-water ratio (CWR). The purpose of this study was to compare the CWR evaluated by using spectroscopic photoacoustic (sPA) imaging in cervical samples obtained from pregnant and non-pregnant women.MethodsThis cross-sectional study comprised cervical biopsies obtained at the time of hysterectomy (n = 8) and at the scheduled cesarean delivery in pregnant women at term who were not in labor (n = 8). The cervical CWR was analyzed using a fiber-optic light-delivery system integrated to an ultrasound probe. The photoacoustic signals were acquired within the range of wavelengths that cover the peak absorption of collagen and water. Differences in the CWR between cervical samples from pregnant and non-pregnant women were analyzed. Hematoxylin and eosin and Sirius Red stains were used to compare the collagen content of cervical samples in these two groups.ResultsEight cervix samples were obtained after hysterectomy, four from women ≤41 years of age and four from women ≥43 years of age; all cervical samples (n = 8) from pregnant women were obtained after 37 weeks of gestation at the time of cesarean section. The average CWR in cervical tissue samples from pregnant women was 18.7% (SD 7.5%), while in samples from non-pregnant women, it was 55.0% (SD 20.3%). There was a significantly higher CWR in the non-pregnant group compared to the pregnant group with a p-value ConclusionThe proposed bimodal ultrasound and sPA imaging system can provide information on the biochemical composition of cervical tissue in pregnant and non-pregnant women. Photoacoustic imaging showed a higher collagen content in cervical samples from non-pregnant women as compared to those from pregnant women, which matched with the histological analysis. This novel imaging method envisions a new potential for a sensitive diagnostic tool in the evaluation of cervical tissue composition