A new method for visualizing pulmonary artery microvasculature using synchrotron radiation pulmonary microangiography: the measurement of pulmonary arterial blood flow velocity in the high pulmonary blood flow rat model.

BACKGROUND: Increased pulmonary blood flow (PBF) and shear stress may provoke irreversible vascular remodeling, yet invasive visualization of the microvasculature complicates monitoring. A non-invasive imaging methodology would therefore safely provide mechanistic insights into the progression of high PBF-induced vascular remodeling. PURPOSE: To establish a novel microvasculature visualization method using synchrotron radiation pulmonary microangiography (SRPA) that can also calculate PBF velocity in vivo. MATERIAL AND METHODS: A high PBF rat model was established by making a fistula between the abdominal aorta and inferior vena cava. After eight weeks, SRPA was performed and the dynamic density changes in the right lower pulmonary artery (PA) were calculated by software. SRPA was performed with a HARP (High-Gain Avalanche Rushing amorphous Photoconductor) receiver. PBF velocity was calculated by contrast medium transit time within the PA. All data were presented as mean ± standard error (SE). Student's t-test was used for comparison between the two groups. RESULTS: High dynamic spatial and contrast resolution from SRPA in the PA allowed for clear pulmonary microangiography and accurate detection of higher PBF in the rat model (82.3 ± 8.5 mm/s high-PBF group vs. 46.1 ± 4.3 mm/s control group, P < 0.01). CONCLUSIONS: These novel results demonstrate that SRPA was useful in both visualizing the dynamic flow distribution within the microvasculature and calculating PBF velocity. This newly developed, non-invasive technology may become a powerful tool in clarifying the mechanism of vascular remodeling associated with high PBF-induced shear stress.

Improved temporal performance and optical quantum efficiency of avalanche amorphous selenium for low dose medical imaging.

Purpose: Active matrix flat panel imagers (AMFPIs) with thin-film transistor arrays experience image quality degradation by electronic noise in low-dose radiography and fluoroscopy. One potential solution is to overcome electronic noise using avalanche gain in an amorphous selenium (a-Se) (HARP) photoconductor in indirect AMFPI. In this work, we aim to improve temporal performance of HARP using a novel composite hole blocking layer (HBL) structure and increase optical quantum efficiency (OQE) to CsI:Tl scintillators by tellurium (Te) doping. Approach: Two different HARP structures were fabricated: Composite HBL samples and Te-doped samples. Dark current and optical sensitivity measurements were performed on the composite HBL samples to evaluate avalanche gain and temporal performance. The OQE and temporal performance of the Te-doped samples were characterized by optical sensitivity measurements. A charge transport model was used to investigate the hole mobility and lifetime of the Te-doped samples in combination with time-of-flight measurements. Results: The composite HBL has excellent temporal performance, with ghosting below 3% at 10 mR equivalent exposure. Furthermore, the composite HBL samples have dark current <10-10 A/cm2 and achieved an avalanche gain of 16. Te-doped samples increased OQE from 0.018 to 0.43 for 532 nm light. The addition of Te resulted in 2.1% first-frame lag, attributed to hole trapping within the layer. Conclusions: The composite HBL and Te-doping can be utilized to improve upon the limitations of previously developed indirect HARP imagers, showing excellent temporal performance and increased OQE, respectively.

Electroded avalanche amorphous selenium (a-Se) photosensor.

Although avalanche amorphous selenium (a-Se) is a very promising photoconductor for a variety of imaging applications, it is currently restricted to applications with electron beam readout in vacuum pick-up tube called a High-gain Avalanche Rushing Photoconductor (HARP). The electron beam readout is compatible with high definition television (HDTV) applications, but for use in solid-state medical imaging devices it should be replaced by an electronic readout with a two-dimensional array of metal pixel electrodes. However, due to the high electric field required for avalanche multiplication, it is a technological challenge to avoid possible dielectric breakdown at the edges, where electric field experiences local enhancement. It has been shown recently that this problem can be overcome by the use of a Resistive Interface Layer (RIL) deposited between a-Se and the metal electrode, however, at that time, at a sacrifice in transport properties.Here we show that optimization of RIL deposition technique allows for electroded avalanche a-Se with transport properties and time performance previously not achievable with any other a-Se structures. We have demonstrated this by detailed analysis of transport properties performed by Time-of-Flight (TOF) technique. Our results showed that a stable gain of 200 is reached at 104 V/µm for a 15-µm thick a-Se layer, which is the maximum theoretical gain for this thickness. We conclude that RIL is an enabling technology for practical implementation of solid-state avalanche a-Se image sensors.

Toward Scintillator High-Gain Avalanche Rushing Photoconductor Active Matrix Flat Panel Imager (SHARP-AMFPI): Initial fabrication and characterization.

PURPOSE: We present the first prototype Scintillator High-Gain Avalanche Rushing Photoconductor Active Matrix Flat Panel Imager (SHARP-AMFPI). This detector includes a layer of avalanche amorphous Selenium (a-Se) (HARP) as the photoconductor in an indirect detector to amplify the signal and reduce the effects of electronic noise to obtain quantum noise-limited images for low-dose applications. It is the first time avalanche a-Se has been used in a solid-state imaging device and poses as a possible solution to eliminate the effects of electronic noise, which is crucial for low-dose imaging performance of AMFPI. METHODS: We successfully deposited a solid-state HARP structure onto a 24 × 30 cm2 array of thin-film transistors (TFT array) with a pixel pitch of 85 µm. The HARP layer consists of 16 µm of a-Se with a hole-blocking and electron-blocking layer to prevent charge injection from the high-voltage bias and pixel electrodes, respectively. An electric field (ESe ) up to 105 V µm-1 was applied across the a-Se layer without breakdown. A 150 µm thick-structured CsI:Tl scintillator was used to form SHARP-AMFPI. The x-ray imaging performance is characterized using a 30 kVp Mo/Mo beam. We evaluate the spatial resolution, noise power, and detective quantum efficiency at zero frequency of the system with and without avalanche gain. The results are analyzed using cascaded linear system model (CLSM). RESULTS: An avalanche gain of 76 ± 5 was measured at ESe = 105 V µm-1 . We demonstrate that avalanche gain can amplify the signal to overcome electronic noise. As avalanche gain is increased, image quality improves for a constant (0.76 mR) exposure until electronic noise is overcome. Our system is currently limited by poor optical transparency of our high-voltage electrode and long integrating time which results in dark current noise. These two effects cause high-spatial frequency noise to dominate imaging performance. CONCLUSIONS: We demonstrate the feasibility of a solid-state HARP x-ray imager and have fabricated the largest active area HARP sensor to date. Procedures to reduce secondary quantum and dark noise are outlined. Future work will improve optical coupling and charge transport which will allow for frequency DQE and temporal metrics to be obtained.

8K ultra-high-definition microscopic camera for ophthalmic surgery.

BACKGROUND: We have developed a new compact lightweight 8K ultra-high-definition (UHD; 7,680×4,320 pixels) camera and started medical application with an ophthalmic surgical microscope which is interchangeable with the conventional high-definition (1,920×1,080 pixels)/4K UHD (3,840×2,160 pixels) microscopic camera. METHODS: We did a feasibility study to apply our 8K UHD microscope in cataract surgery, glaucoma surgery and vitreous surgery using pig cadaver eyes. The 8K UHD microscope comprises a surgical microscope, a camera adaptor with relay lenses, an 8K UHD camera and an 8K UHD LCD to share the 8K UHD images with all surgical staff in real time. RESULTS: In ophthalmic surgeries, higher resolution images than conventional microscopic cameras were obtained with 8K UHD LCD equivalent to the observation through the microscopic eye pieces. CONCLUSION: Based on the results of this feasibility study, clinical trials on human ophthalmic surgery using the new 8K UHD microscopic camera should be conducted in the near future.

X-ray imaging using avalanche multiplication in amorphous selenium: investigation of intrinsic avalanche noise.

The flat-panel detector (FPD) is the state-of-the-art detector for digital radiography. The FPD can acquire images in real-time, has superior spatial resolution, and is free of the problems of x-ray image intensifiers-veiling glare, pin-cushion and magnetic distortion. However, FPDs suffer from poor signal to noise ratio performance at typical fluoroscopic exposure rates where the quantum noise is reduced to the point that it becomes comparable to the fixed electronic noise. It has been shown previously that avalanche multiplication gain in amorphous selenium (a-Se) can provide the necessary amplification to overcome the electronic noise of the FPD. Avalanche multiplication, however, comes with its own intrinsic contribution to the noise in the form of gain fluctuation noise. In this article a cascaded systems analysis is used to present a modified metric related to the detective quantum efficiency. The modified metric is used to study a diagnostic x-ray imaging system in the presence of intrinsic avalanche multiplication noise independently from other noise sources, such as electronic noise. An indirect conversion imaging system is considered to make the study independent of other avalanche multiplication related noise sources, such as the fluctuations arising from the depth of x-ray absorption. In this case all the avalanche events are initiated at the surface of the avalanche layer, and there are no fluctuations in the depth of absorption. Experiments on an indirect conversion x-ray imaging system using avalanche multiplication in a layer of a-Se are also presented. The cascaded systems analysis shows that intrinsic noise of avalanche multiplication will not have any deleterious influence on detector performance at zero spatial frequency in x-ray imaging provided the product of conversion gain, coupling efficiency, and optical quantum efficiency are much greater than a factor of 2. The experimental results show that avalanche multiplication in a-Se behaves as an intrinsic noise free avalanche multiplication, in accordance with our theory. Provided good coupling efficiency and high optical quantum efficiency are maintained, avalanche multiplication in a-Se has the potential to increase the gain and make negligible contribution to the noise, thereby improving the performance of indirect FPDs in fluoroscopy.

X-ray imaging using avalanche multiplication in amorphous selenium: investigation of depth dependent avalanche noise.

The past decade has seen the swift development of the flat-panel detector (FPD), also known as the active matrix flat-panel imager, for digital radiography. This new technology is applicable to other modalities, such as fluoroscopy, which require the acquisition of multiple images, but could benefit from some improvements. In such applications where more than one image is acquired less radiation is available to form each image and amplifier noise becomes a serious problem. Avalanche multiplication in amorphous selenium (a-Se) can provide the necessary amplification prior to read out so as to reduce the effect of electronic noise of the FPD. However, in direct conversion detectors avalanche multiplication can lead to a new source of gain fluctuation noise called depth dependent avalanche noise. A theoretical model was developed to understand depth dependent avalanche noise. Experiments were performed on a direct imaging system implementing avalanche multiplication in a layer of a-Se to validate the theory. For parameters appropriate for a diagnostic imaging FPD for fluoroscopy the detective quantum efficiency (DQE) was found to drop by as much as 50% with increasing electric field, as predicted by the theoretical model. This drop in DQE can be eliminated by separating the collection and avalanche regions. For example by having a region of low electric field where x rays are absorbed and converted into charge that then drifts into a region of high electric field where the x-ray generated charge undergoes avalanche multiplication. This means quantum noise limited direct conversion FPD for low exposure imaging techniques are a possibility.

Ultra-high definition (8K UHD) endoscope: our first clinical success.

BACKGROUND: We have started clinical application of 8K ultra-high definition (UHD; 7680 × 4320 pixels) imaging technology, which is a 16-fold higher resolution than the current 2K high-definition (HD; 1920 × 1080 pixels) technology, to an endoscope for advanced laparoscopic surgery. RESULTS: Based on preliminary testing experience and with subsequent technical and system improvements, we then proceeded to perform two cases of cholecystectomy and were able to achieve clinical success with an 8K UHD endoscopic system, which consisted of an 8K camera, a 30-degrees angled rigid endoscope with a lens adapter, a pair of 300-W xenon light sources, an 85-inch 8K LCD and an 8K video recorder. These experimental and clinical studies revealed the engineering and clinical feasibility of the 8K UHD endoscope, enabling us to have a positive outlook on its prospective use in clinical practice. CONCLUSIONS: The 8K UHD endoscopy promises to open up new possibilities for intricate procedures including anastomoses of thin nerves and blood vessels as well as more confident surgical resections of a diversity of cancer tissues. 8K endoscopic imaging, compared to imaging by the current 2K imaging technology, is very likely to lead to major changes in the future of medical practice.

Association between endothelial function and micro-vascular remodeling measured by synchrotron radiation pulmonary micro-angiography in pulmonary arterial hypertension.

OBJECTIVES: Pulmonary arterial hypertension (PAH) is a progressive disease which causes increased vascular resistance. In this study, our purpose was to quantify the micro-vascular remodeling in monocrotaline-induced PAH rats using synchrotron radiation pulmonary micro-angiography (SRPA), a method we have previously established in an in vivo rat model. To determine the relationship between endothelial function and vascular remodeling, the local expression of endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) was evaluated using immunohistochemical staining. METHODS: Monocrotaline-induced PAH rats were created by subcutaneous injection of monocrotaline. After 2 weeks, SRPA was performed at the Photon Factory of the High Energy Accelerator Research Organization. The internal diameters of pulmonary arterioles were measured using SRPA images. Semi-quantified analyses of ET-1, eNOS and VEGF expression in pulmonary arterioles were performed by immunohistochemical staining. RESULTS: Micro-vascular density and the internal diameters of pulmonary arterioles were significantly decreased in PAH. ET-1 expression was significantly increased in PAH compared with the control (1.53 ± 0.45 vs. 0.80 ± 0.14) and eNOS expression was significantly decreased in PAH compared with the control (1.12 ± 0.59 vs. 1.91 ± 0.66), although VEGF expression did not differ between the groups. CONCLUSIONS: SRPA can be effectively used for visualizing the decreased pulmonary micro-vasculature associated with PAH. Increased ET-1 expression and decreased eNOS expression may contribute to the proliferation and vasospasm of pulmonary arterioles induced by endothelial dysfunction due to PAH. This SRPA technology may help to identify a correlation between endothelial function and micro-vasculature remodeling in PAH.

Indirect flat-panel detector with avalanche gain: fundamental feasibility investigation for SHARP-AMFPI (scintillator HARP active matrix flat panel imager).

An indirect flat-panel imager (FPI) with avalanche gain is being investigated for low-dose x-ray imaging. It is made by optically coupling a structured x-ray scintillator CsI(Tl) to an amorphous selenium (a-Se) avalanche photoconductor called HARP (high-gain avalanche rushing photoconductor). The final electronic image is read out using an active matrix array of thin film transistors (TFT). We call the proposed detector SHARP-AMFPI (scintillator HARP active matrix flat panel imager). The advantage of the SHARP-AMFPI is its programmable gain, which can be turned on during low dose fluoroscopy to overcome electronic noise, and turned off during high dose radiography to avoid pixel saturation. The purpose of this paper is to investigate the important design considerations for SHARP-AMFPI such as avalanche gain, which depends on both the thickness d(Se) and the applied electric field E(Se) of the HARP layer. To determine the optimal design parameter and operational conditions for HARP, we measured the E(Se) dependence of both avalanche gain and optical quantum efficiency of an 8 microm HARP layer. The results were used in a physical model of HARP as well as a linear cascaded model of the FPI to determine the following x-ray imaging properties in both the avalanche and nonavalanche modes as a function of E(Se): (1) total gain (which is the product of avalanche gain and optical quantum efficiency); (2) linearity; (3) dynamic range; (4) gain nonuniformity resulting from thickness nonuniformity; and (5) effects of direct x-ray interaction in HARP. Our results showed that a HARP layer thickness of 8 microm can provide adequate avalanche gain and sufficient dynamic range for x-ray imaging applications to permit quantum limited operation over the range of exposures needed for radiography and fluoroscopy.

Inhomogeneous vasodilatory responses of rat tail arteries to heat stress: evaluation by synchrotron radiation microangiography.

Tail blood flow is crucial for dissipating body heat in rats. Angiographies are convenient tools to evaluate tail circulation. However, conventional angiographies do not have sufficient sensitivity or spatial resolution for small vessels. Recently, we developed a novel microangiographic system using monochromatic synchrotron radiation and a high-definition video camera system. Here, we report an evaluation of rat tail circulation under heat stress using the synchrotron radiation microangiographic system. We performed an experiment using the microangiography of the caudal artery before and after heating up WKAH/HkmSlc rats to rectal temperature of 39 degrees C. The images were digitized and temporal subtraction was performed, and the diameters of caudal arteries were evaluated. After heating, the medial caudal artery was markedly dilated (320 +/- 53 to 853 +/- 243 micro m in diameter, p<0.001), while no significant change was observed in the lateral caudal arteries (139 +/- 42 to 167 +/- 73 micro m) and segmental anastomosing vessels. The heat stress allowed for visualization of the superficial caudal arteries with a diameter of approximately 60 micro m, not visible prior to heating. Thus, synchrotron radiation microangiography demonstrated that the rat tail possessed dual sets of arteries; one set was highly sensitive to heat-induced vasodilation (medial caudal artery and superficial caudal arteries) and the other set was less sensitive (lateral caudal arteries and segmental anastomosing vessels).

Development of an X-ray HARP-FEA detector system for high-throughput protein crystallography.

A new detector system for protein crystallography is now being developed based on an X-ray HARP-FEA (high-gain avalanche rushing amorphous photoconductor-field emitter array), which consists of an amorphous selenium membrane and a matrix field emitter array. The combination of the membrane avalanche effect with a single driven FEA has several advantages over currently available area detectors, including higher sensitivity, higher spatial resolution and a higher frame rate. Preliminary evaluation of the detector has been carried out and its effectiveness has been confirmed. Next, diffraction images were measured with continuous rotation of a protein crystal, and the images were compared with those measured by the existing CCD detector; the system successfully obtained high-spatial-resolution images. Using shutterless measurement, the total measurement time can be reduced significantly, making the method appropriate for high-throughput protein crystallography. The X-ray HARP-FEA detector is an attractive candidate for the next generation of X-ray area detectors.

An aluminum influence on root circumnutation in dark revealed by a new super-HARP (high-gain avalanche rushing amorphous photoconductor) camera.

The circumnutation of a rice root under dark conditions was observed using a highly sensitive camera, a new super-HARP camera. A rice root showed regular rhythmic movement with fixed angle. When treated with Al (5 microM AlCl3), the rotation angle of the root tip was drastically decreased and then the movement was resumed again, whereas the root elongation rate was constant. With the increase of Al concentration, the cycle-fading period became shorter. This is the first report to show that an Al treatment ceased the rotation movement of the root but not elongation.