Correction of a transcranial acoustic field using a transient ultrasound field visualization technique.

Ultrasound, due to its noninvasive nature, has the potential to enhance or suppress neural activity, making it highly promising for regulating intractable brain disorders. Precise ultrasound stimulation is crucial for improving the efficiency of neural modulation and studying its mechanisms. However, the presence of the skull can cause distortion in the ultrasound field, thereby affecting the accuracy of stimulation. Existing correction methods primarily rely on magnetic resonance guidance and numerical simulation. Due to the large size and high cost, the MR-guided transcranial ultrasound is difficult to be widely applied in small animals. The numerical simulation usually requires further validation and optimization before application, and the most effective method is to visualize the excited ultrasound field. However, the ultrasound field correction methods based on acoustic field visualization are still lacking. Therefore, a shadowgraph-based transient ultrasonic field visualization system is developed, and an ex vivo transcranial ultrasound field correction is performed. By visualizing the ultrasound field with or without a rat skull and then calculating the time difference of each element's ultrasound wavefront, the parameters for ultrasound field correction can be achieved. The experimental results show that this method can improve both the shape and the size of the focal spot, as well as enhance the acoustic pressure at the focus. Overall, the results demonstrate that the ultrasonic field visualization technology can effectively improve the transcranial ultrasound focusing effect and provide a new tool for achieving precise ultrasonic neural modulation.

Photoacoustic maximum amplitude projection microscopy by ultra-low data sampling.

Photoacoustic microscopy (PAM) has attracted increasing research interest in the biomedical field due to its unique merit of combining light and sound. In general, the bandwidth of a photoacoustic signal reaches up to tens or even hundreds of MHz, which requires a high-performance acquisition card to meet the high requirement of precision of sampling and control. For most depth-insensitive scenes, it is complex and costly to capture the photoacoustic maximum amplitude projection (MAP) images. Herein, we propose a simple and low-cost MAP-PAM system based on a custom-made peak holding circuit to obtain the extremum values by Hz data sampling. The dynamic range of the input signal is 0.01-2.5 V, and the -6-dB bandwidth of the input signal can be up to 45 MHz. Through in vitro and in vivo experiments, we have verified that the system has the same imaging ability as conventional PAM. Owing to its compact size and ultra-low price (approximately $18), it provides a new performance paradigm for PAM and opens up a new way for an optimal photoacoustic sensing and imaging device.

Voltage-Gated Na+ Channels are Modulated by Glucose and Involved in Regulating Cellular Insulin Content of INS-1 Cells.

BACKGROUND/AIMS: Islet beta cells (ß-cells) are unique cells that play a critical role in glucose homeostasis by secreting insulin in response to increased glucose levels. Voltage-gated ion channels in ß-cells, such as K+ and Ca2+ channels, contribute to insulin secretion. The response of voltage-gated Na+ channels (VGSCs) in ß-cells to the changes in glucose levels remains unknown. This work aims to determine the role of extracellular glucose on the regulation of VGSC. METHODS: The effect of glucose on VGSC currents (INa) was investigated in insulin-secreting ß-cell line (INS-1) cells of rats using whole-cell patch clamp techniques, and the effects of glucose on insulin content and cell viability were determined using Enzyme-Linked Immunosorbent Assay (ELISA) and Methylthiazolyldiphenyl-tetrazolium Bromide (MTT) assay methods respectively. RESULTS: Our results show that extracellular glucose application can inhibit the peak of INa in a concentration-dependent manner. Glucose concentration of 18 mM reduced the amplitude of INa, suppressed the INa of steady-state activation, shifted the steady-state inactivation curves of INa to negative potentials, and prolonged the time course of INa recovery from inactivation. Glucose also enhanced the activity-dependent attenuation of INa and reduced the fraction of activated channels. Furthermore, 18 mM glucose or low concentration of tetrodotoxin (TTX, a VGSC-specific blocker) partially inhibited the activity of VGSC and also improved insulin synthesis. CONCLUSION: These results revealed that extracellular glucose application enhances the insulin synthesis in INS-1 cells and the mechanism through the partial inhibition on INa channel is involved. Our results innovatively suggest that VGSC plays a vital role in modulating glucose homeostasis.

Label-free optical-resolution photoacoustic microscopy of superficial microvasculature using a compact visible laser diode excitation.

We have developed laser-diode-based optical-resolution photoacoustic microscopy (LD-OR-PAM) of superficial microvasculature which has the desirable properties of being compact, low-cost, and label-free. A 300-mW visible pulsed laser diode was operated at a 405 ± 5 nm wavelength with a pulse energy as low as 52 nJ. By using a 3.6 MHz ultrasound transducer, the system was tested on carbon fibers with a lateral resolution of 0.95 µm and an SNR of 38 dB. The subcutaneous microvasculature on a mouse back was imaged without an exogenous contrast agent which demonstrates the potential of the proposed prototype for skin chromophores. Our eventual goal is to offer a practical and affordable multi-wavelength functional LD-OR-PAM instrument suitable for clinical applications.

Noninvasive photoacoustic detecting intraocular foreign bodies with an annular transducer array.

We present a fast photoacoustic imaging system based on an annular transducer array for detection of intraocular foreign bodies. An eight-channel data acquisition system is applied to capture the photoacoustic signals using multiplexing and the total time of data acquisition and transferring is within 3 s. A limited-view filtered back projection algorithm is used to reconstruct the photoacoustic images. Experimental models of intraocular metal and glass foreign bodies were constructed on ex vivo pig's eyes and clear photoacoustic images of intraocular foreign bodies were obtained. Experimental results demonstrate the photoacoustic imaging system holds the potential for in clinic detecting the intraocular foreign bodies.

Transcranial ultrasound stimulation relieves depression in mice with chronic restraint stress.

Objective.Exhaustion of Serotonin (5-hydroxytryptamine, 5-HT) is a typical cause of the depression disorder's development and progression, including depression-like behaviors. Transcranial ultrasound stimulation (TUS) is an emerging non-invasive neuromodulation technique treating various neurodegenerative diseases. This study aims to investigate whether TUS ameliorates depression-like behaviors by restoring 5-HT levels.Methods.The depression model mice are established by chronic restraint stress (CRS). Ultrasound waves (FF = 1.1 MHz, PRF = 1000 Hz, TBD = 0.5 ms, SD = 1 s, ISI = 1 s, and DC = 50%) were delivered into the dorsal raphe nucleus (DRN) for 30 min per day for 2 weeks. Depression-like behavior changes are evaluated with the sucrose preference and tail suspension tests. Liquid chromatography-mass spectrometry is performed to quantitatively detect the concentration of 5-HT in the DRN to explore its potential mechanism. The effectiveness and safety of TUS were assessed by c-Fos immunofluorescence and hematoxylin and eosin (HE) staining, respectively.Results.Three weeks after CRS, 22 depressive mice models were screened by sucrose preference index (SPI). After 2 weeks of ultrasound stimulation of the DRN (DRN-TUS) in depressive mice, the SPI was increased (p= 0.1527) and the tail suspension immobility duration was significantly decreased (p= 0.0038) compared with the non-stimulated group. In addition, TUS significantly enhances the c-Fos (p= 0.05) positive cells' expression and the 5-HT level (p= 0.0079) in the DRN. Importantly, HE staining shows no brain tissue damage.Conclusion.These results indicate that DRN-TUS has safely and effectively improved depression-like behaviors including anhedonia and hopelessness, potentially by reversing the depletion of 5-TH.SignificanceTUS may provide a new perspective on depression therapy, possibly through restoring monoamine levels.

Transcranial ultrasound neuromodulation facilitates isoflurane-induced general anesthesia recovery and improves cognition in mice.

Delayed arousal and cognitive dysfunction are common, especially in older patients after general anesthesia (GA). Elevating central nervous system serotonin (5-HT) levels can promote recovery from GA and increase synaptic plasticity to improve cognition. Ultrasound neuromodulation has become a noninvasive physical intervention therapy with high spatial resolution and penetration depth, which can modulate neuronal excitability to treat psychiatric and neurodegenerative diseases. This study aims to use ultrasound to noninvasively modulate the brain 5-HT levels of mice to promote recovery from GA and improve cognition in mice. The dorsal raphe nucleus (DRN) of mice during GA was stimulated by the 1.1 MHz ultrasound with a negative pressure of 356 kPa, and the liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) method was used to measure the DRN 5-HT concentrations. The mice's recovery time from GA was assessed, and the cognition was evaluated through spontaneous alternation Y-maze and novel object recognition (NOR) tests. After ultrasound stimulation, the mice's DRN 5-HT levels were significantly increased (control: 554.0 ± 103.2 ng/g, anesthesia + US: 664.2 ± 84.1 ng/g, *p = 0.0389); the GA recovery time (return of the righting reflex (RORR) emergence latency time) of mice was significantly reduced (anesthesia: 331.6 ± 70 s, anesthesia + US: 223.2 ± 67.7 s, *p = 0.0215); the spontaneous rotation behavior score of mice was significantly increased (anesthesia: 59.46 ± 5.26 %, anesthesia + US: 68.55 ± 5.24 %; *p = 0.0126); the recognition index was significantly increased (anesthesia: 55.02 ± 6.23 %, anesthesia + US: 78.52 ± 12.21 %; ***p = 0.0009). This study indicates that ultrasound stimulation of DRN increases serotonin levels, accelerates recovery from anesthesia, and improves cognition, which could be an important strategy for treating delayed arousal, postoperative delirium, or even lasting cognitive dysfunction after GA.

Simultaneous multi-target ultrasound neuromodulation in freely-moving mice based on a single-element ultrasound transducer.

Objective.Ultrasound neuromodulation has become an emerging method for the therapy of neurodegenerative and psychiatric diseases. The phased array ultrasonic transducer enables multi-target ultrasound neuromodulation in small animals, but the relatively large size and mass and the thick cables of the array limit the free movement of small animals. Furthermore, spatial interference may occur during multi-target ultrasound brain stimulation with multiple micro transducers.Approach.In this study, we developed a miniature power ultrasound transducer and used the virtual source time inversion method and 3D printing technology to design, optimize, and manufacture the acoustic holographic lens to construct a multi-target ultrasound neuromodulation system for free-moving mice. The feasibility of the system was verified byin vitrotranscranial ultrasound field measurements,in vivodual-target blood-brain barrier (BBB) opening experiments, andin vivodual-target ultrasound neuromodulation experiments.Main results.The developed miniature transducer had a diameter of 4.0 mm, a center frequency of 1.1 MHz, and a weight of 1.25 g. The developed miniature acoustic holographic lens had a weight of 0.019 g to generate dual-focus transcranial ultrasound. The ultrasonic field measurements' results showed that the bifocal's horizontal distance was 3.0 mm, the -6 dB focal spot width in thex-direction was 2.5 and 2.25 mm, and 2.12 and 2.24 mm in they-direction. Finally, thein vivoexperimental results showed that the system could achieve dual-target BBB opening and ultrasound neuromodulation in freely-moving mice.Significance.The ultrasonic neuromodulation system based on a miniature single-element transducer and the miniature acoustic holographic lens could achieve dual-target neuromodulation in awake small animals, which is expected to be applied to the research of non-invasive dual-target ultrasonic treatment of brain diseases in awake small animals.

Ultrasound neuromodulation ameliorates chronic corticosterone-induced depression- and anxiety-like behaviors in mice.

Objective.Monoamine dysfunction has been implicated as a pathophysiological basis of several mental disorders, including anxiety and depression. Transcranial ultrasound stimulation (TUS) is a noninvasive nerve stimulation technic showing great potential in treating depression/anxiety disorders. This study aims to investigate whether TUS can ameliorate depression with anxiety in mice by regulating brain monoamine levels.Approach.Mice received repeated subcutaneous injections of corticosterone (CORT, 20 mg kg-1) for 3 weeks to produce depression- and anxiety-like behaviors. Ultrasound stimulated the dorsal lateral nucleus (DRN) for 30 min daily for 3 weeks without interruption of CORT injection. Behavioral phenotypes of depression and anxiety were estimated by sucrose preference test (SPT), tail suspension test (TST), and elevated plus-maze test (EPM). Liquid chromatography-mass spectrometry (LC-MS) was used to quantify brain levels of serotonin (5-HT), norepinephrine (NE), and dopamine (DA). Western blotting was performed to detect brain-derived neurotrophic factor (BDNF) levels in hippocampal.Main results.TUS of DRN significantly ameliorated the depression-like behaviors in SPT (p= 0.0004) and TST (p= 0.0003) as well as anxiety-like behaviors in EPM (open arm entry frequencies,p< 0.05). Moreover, TUS increased c-Fos-positive cell expression (p= 0.0127) and induced no tissue damage. LC-MS results showed TUS of DRN resulted in a non-significant increase in the 5-HT levels and a significant decrease in the NE levels, but did not affect the levels of DA and BDNF.Significance.These results suggest TUS of DRN has safely and effectively ameliorated CORT-induced depression- and anxiety-like behaviors, possibly by restoring brain levels of 5-HT and NE. TUS may be a safe and effective technique for remedying depression and anxiety comorbidity.

3D-visual laser-diode-based photoacoustic imaging.

We present a 3D-visual laser-diode-based photoacoustic imaging (LD-PAI) system with a pulsed semiconductor laser source, which has the properties of being inexpensive, portable, and durable. The laser source was operated at a wavelength of 905 nm with a repetition rate of 0.8 KHz. The energy density on the sample surface is about 2.35 mJ/cm(2) with a pulse energy as low as 5.6 µJ. By raster-scanning, preliminary 3D volumetric renderings of the knotted and helical blood vessel phantoms have been visualized integrally with an axial resolution of 1.1 mm and a lateral resolution of 0.5 mm, and typical 2D photoacoustic image slices with different thickness and orientation were produced with clarity for detailed comparison and analysis in 3D diagnostic visualization. In addition, the pulsed laser source was integrated with the optical lens group and the 3D adjustable rotational stage, with the result that the compact volume of the total radiation source is only 10 × 3 × 3 cm(3). Our goal is to significantly reduce the costs and sizes of the deep 3D-visual PAI system for future producibility.

Multitarget Transcranial Ultrasound Therapy in Small Animals Based on Phase-Only Acoustic Holographic Lens.

Transcranial ultrasound therapy has become a noninvasive method for treating neurological and psychiatric disorders, and studies have further demonstrated that multitarget transcranial ultrasound therapy is a better solution. At present, multitarget transcranial ultrasound therapy in small animals can only be achieved by the multitransducer or phased array. However, multiple transducers may cause spatial interference, and the phased array system is complicated, expensive, and especially unsuitable for small animals. This study is the first to design and fabricate a miniature acoustic holography lens for multitarget transcranial ultrasound therapy in rats. The acoustic holographic lens, working at a frequency of 1.0 MHz, with a size of 10.08 mm ×10.08 mm and a pixel resolution of 0.72 mm, was designed, optimized, and fabricated. The dual-focus transcranial ultrasound generated based on the lens was measured; the full-width at half-maximum (FWHM) of the focal spots in the y -direction was 2.15 and 2.27 mm and in the z -direction was 2.3 and 2.36 mm. The focal length was 5.4 mm, and the distance between the two focuses was 5.6 mm, close to the desired values of 5.4 and 6.0 mm. Finally, the multiple-target blood-brain barrier opening in rats' bilateral secondary visual cortex (mediolateral area, V2ML) was demonstrated using the transcranial ultrasound therapy system based on the lens. These results demonstrate the good performance of the multitarget transcranial ultrasound therapy system for small animals, including high spatial resolution, small size, and low cost.

In vivo quantitative photoacoustic evaluation of the liver and kidney pathology in tyrosinemia.

Hereditary tyrosinemia type Ⅰ (HT1) is a severe autosomal recessive inherited metabolic disease, which can result in severe damage of liver and kidney. Photoacoustic imaging (PAI) uses pulsed laser light to induce ultrasonic signals to facilitate the visualization of lesions that are strongly related to disease progression. In this study, the structural and functional changes of liver and kidney in HT1 was investigated by cross-scale PAI. The results showed that the hepatic lobule and renal tubule were severely damaged during HT1 progression. The hemoglobin content, vessel density, and liver function reserve were decreased. The metabolic half-life of indocyanine green declined from 59.8 s in health to 262.6 s in the advanced stage. Blood oxygen saturation was much lower than that in health. This study highlights the potential of PAI for in vivo evaluation of the liver and kidney lesions in HT1.

A Spatial Multitarget Ultrasound Neuromodulation System Using High-Powered 2-D Array Transducer.

Transcranial focused ultrasound (tFUS) is increasingly used in experimental neuroscience due to its neuromodulatory effectiveness in animal studies. However, achieving multitarget tFUS in small animals is typically limited by transducer size, energy transfer efficiency, and brain volume. The objective of this work was to construct an ultrasound system for multitarget neuromodulation in small animals. First, a miniaturized high-powered 2-D array transducer was developed. The phase delay of each array element was calculated based on the multifocal time-reversal method, generating multiple foci simultaneously in a 3-D field. The effects of the axial focal length, interfocus spacing (lateral distance between the two focal centers), and the number of foci on the focal properties of the pressure field were examined through numerical simulations. In-vitro ultrasonic measurements and transcranial simulations on a rat skull were conducted. The minimum interfocus spacing separating two -6-dB foci and the peak full-width at half-maximum were positively correlated with axial focal length; the relative relationship between the interfocus spacing and pressure field properties was similar for each axial focal length. The maximum acoustic pressure and spatial average intensity at focus in deionized water were 2.21 MPa and 133 W/cm2, respectively. The simulated and experimental results were compared, demonstrating agreement in both peak position and focus shape. The ultrasound system can provide a neuroscientific platform for evaluating the feasibility of multitarget ultrasound stimulation treatment protocols, thus improving the understanding of functional neuroanatomy.

Centimeter-scale wide-field-of-view laser-scanning photoacoustic microscopy for subcutaneous microvasculature in vivo.

We developed a simple and compact laser-scanning photoacoustic microscopy (PAM) for imaging large areas of subcutaneous microvasculature in vivo. The reflection-mode PAM not only retains the advantage of high scanning speed for optical scanning, but also offers an imaging field-of-view (FOV) up to 20 × 20 mm2, which is the largest FOV available in laser-scanning models so far. The lateral resolution of the PAM system was measured to be 17.5 µm. Image experiments on subcutaneous microvasculature in in vivo mouse ears and abdomen demonstrate the system's potential for fast and high-resolution imaging for injuries and diseases of large tissues and organs.

Micromachining of High Quality PMN-31%PT Single Crystals for High-Frequency (>20 MHz) Ultrasonic Array Transducer Applications.

A decrease of piezoelectric properties in the fabrication of ultra-small Pb(Mg1/3Nb2/3)-x%PbTiO3 (PMN-x%PT) for high-frequency (>20 MHz) ultrasonic array transducers remains an urgent problem. Here, PMN-31%PT with micron-sized kerfs and high piezoelectric performance was micromachined using a 355 nm laser. We studied the kerf profile as a function of laser parameters, revealing that micron-sized kerfs with designated profiles and fewer micro-cracks can be obtained by optimizing the laser parameters. The domain morphology of micromachined PMN-31%PT was thoroughly analyzed to validate the superior piezoelectric performance maintained near the kerfs. A high piezoresponse of the samples after micromachining was also successfully demonstrated by determining the effective piezoelectric coefficient (d33*~1200 pm/V). Our results are promising for fabricating superior PMN-31%PT and other piezoelectric high-frequency (>20 MHz) ultrasonic array transducers.

In vivo monitoring the dynamic process of acute retinal hemorrhage and repair in zebrafish with spectral-domain optical coherence tomography.

Retina, the only light sensor in the human eye, is hidden and extremely fragile. Optimized animal models and efficient imaging techniques are very important for the study of retinopathy. In this work, the rapid retinal injury process and the long-term retinal repair process were in vivo continuously evaluated with a novel imaging technology spectral-domain optical coherence tomography (SD-OCT) in a unique animal model zebrafish. Acute retinal injury was constructed on adult zebrafish by needle injection surgery. SD-OCT imaging was carried out immediately after the mechanical injury. The retinal hemorrhage, which lasted only 5 seconds, could be visualized dynamically by SD-OCT. The process of blood clearance and retinal repair was also evaluated because SD-OCT imaging is nondestructive. Both SD-OCT imaging results and behavioral analyzing results demonstrated that zebrafish retina could be repaired by itself within 15 days, which was confirmed by the results of pathological experiment.

In vivo monitoring and high-resolution characterizing of the prednisolone-induced osteoporotic process on adult zebrafish by optical coherence tomography.

Because of its similar genetic makeup with humans, zebrafish are an available and well-established osteoporosis model in vivo for anti-osteoporosis drug development as well as the drug safety-evaluation process. However, few optical imaging methods could effectively visualize the bone of adult zebrafish due to their limited penetration depth. In this paper, in vivo high-resolution and long-term characterization of a prednisolone-induced osteoporotic zebrafish model was achieved with spectral-domain optical coherence tomography (SD-OCT). The capability of three-dimensional SD-OCT imaging was also demonstrated in this study. With SD-OCT images, we could non-destructively monitor the deforming process of adult zebrafish skull from several directions at any time. There is good correlation and agreement between SD-OCT and histology. Valuable phenomenon such as bone defects could be quantitatively evaluated using the SD-OCT images at different time points during a period of 21 days.

Effects of polysaccharide from Portulaca oleracea L. on voltage-gated Na+ channel of INS-1 cells.

Our previous work showed that polysaccharide isolated from Portulaca oleracea L. (POP) has an insulinotropic effect. The voltage-gated Na+ channel (VGSC) in the excitement phase plays an important role. This work aims to study the effect of POP on the voltage-gated Na+ channel current (INa) and its channel dynamic characteristics in insulin-secreting ß-cell line (INS-1) cells of rat. Our results revealed that POP can inhibit the amplitude of INa and improve cell survival in a concentration-dependent manner. POP concentration of 0.5 mg mL-1 reduced the amplitude of INa, suppressed the INa of steady-state activation, shifted the steady-state inactivation curves of INa to negative potentials, prolonged the time course of INa recovery from inactivation, and enhanced the activity-dependent attenuation of INa. Furthermore, 0.5 mg mL-1 POP or low concentration of tetrodotoxin (TTX, a VGSC-specific blocker) partially inhibited INa and also improved insulin synthesis and cell survival. Collectively, these results revealed that POP protects INS-1 cells and enhances the insulin synthesis in INS-1 cells, and the mechanism through the partial inhibition on INa channel is strongly recommended.

Real-time optoacoustic monitoring of vascular damage during photodynamic therapy treatment of tumor.

The optoacoustic technique is a noninvasive imaging method with high spatial resolution. It potentially can be used to monitor anatomical and physiological changes. Photodynamic therapy (PDT)-induced vascular damage is one of the important mechanisms of tumor destruction, and real-time monitoring of vascular changes can have therapeutic significance. A unique optoacoustic system is developed for neovascular imaging during tumor phototherapy. In this system, a single-pulse laser beam is used as the light source for both PDT and for concurrently generating ultrasound signals for optoacoustic imaging. To demonstrate its feasibility, this system is used to observe vascular changes during PDT treatment of chicken chorioallantoic membrane (CAM) tumors. The photosensitizer used in this study is protoporphyrin IX (PpIX) and the laser wavelength is 532 nm. Neovascularization in tumor angiogenesis is visualized by a series of optoacoustic images at different stages of tumor growth. Damage of the vascular structures by PDT is imaged before, during, and after treatment. Rapid, real-time determination of the size of targeted tumor blood vessels is achieved, using the time difference of positive and negative ultrasound peaks during the PDT treatment. The vascular effects of different PDT doses are also studied. The experimental results show that a pulsed laser can be conveniently used to hybridize PDT treatment and optoacoustic imaging and that this integrated system is capable of quantitatively monitoring the structural change of blood vessels during PDT. This method could be potentially used to guide PDT and other phototherapies using vascular changes during treatment to optimize treatment protocols, by choosing appropriate types and doses of photosensitizers and doses of light.

High antinoise photoacoustic tomography based on a modified filtered backprojection algorithm with combination wavelet.

How to extract the weak photoacoustic signals from the collected signals with high noise is the key to photoacoustic signal processing. We have developed a modified filtered backprojection algorithm based on combination wavelet for high antinoise photoacoustic tomography. A Q-switched-Nd: yttrium-aluminum-garnet laser operating at 532 nm is used as light source. The laser has a pulse width of 7 ns and a repetition frequency of 20 Hz. A needle polyvinylidene fluoride hydrophone with diameter of 1 mm is used to capture photoacoustic signals. The modified algorithm is successfully applied to imaging vascular network of a chick embryo chorioallantoic membrane in situ and brain structure of a rat brain in vivo, respectively. In the reconstructed images, almost all of the capillary vessels and the vascular ramifications of the chick embryo chorioallantoic membrane are accurately resolved, and the detailed brain structures of the rat brain organization are clearly identified with the skull and scalp intact. The experimental results demonstrate that the modified algorithm has much higher antinoise capacity, and can greatly improve the reconstruction image quality. The spatial resolution of the reconstructed images can reach 204 microm. The modified filtered back-projection algorithm based on the combination wavelet has the potential in the practical high-noise signal processing for deeply penetrating photoacoustic tomography.