Detection and quantification of myocardial reperfusion hemorrhage using T2*-weighted CMR.

OBJECTIVES: The purpose of this study was to validate T2*-weighted cardiac magnetic resonance (T2*-CMR) for the detection and quantification of reperfusion hemorrhage in vivo against an ex vivo gold standard, and to investigate the relationship of hemorrhage to microvascular obstruction, infarct size, and left ventricular (LV) functional parameters. BACKGROUND: Hemorrhage can contribute to reperfusion injury in myocardial infarction and may have significant implications for patient management. There is currently no validated imaging method to assess reperfusion hemorrhage in vivo. T2*-CMR appears suitable because it can create image contrast on the basis of magnetic field effects of hemoglobin degradation products. METHODS: In 14 mongrel dogs, myocardial infarction was experimentally induced. On day 3 post-reperfusion, an in vivo CMR study was performed including a T2*-weighted gradient-echo imaging sequence for hemorrhage, standard sequences for LV function, and post-contrast sequences for microvascular obstruction and myocardial necrosis. Ex vivo, thioflavin S imaging and triphenyl-tetrazoliumchloride (TTC) staining were performed to assess microvascular obstruction, hemorrhage, and myocardial necrosis. Images were analyzed by blinded observers, and comparative statistics were performed. RESULTS: Hemorrhage occurred only in the dogs with the largest infarctions and the greatest extent of microvascular obstruction, and it was associated with more compromised LV functional parameters. Of 40 hemorrhagic segments on TTC staining, 37 (92.5%) were positive for hemorrhage on T2*-CMR (kappa = 0.96, p < 0.01 for in vivo/ex vivo segmental agreement). The amount of hemorrhage in 13 affected tissue slices as determined by T2*-CMR in vivo correlated strongly with ex vivo results (20.3 ± 2.3% vs. 17.9 ± 1.6% per slice; Pearson r = 0.91; r(2) = 0.83, p < 0.01 for both). Hemorrhage size was not different between in vivo T2*-CMR and ex vivo TTC (mean difference 2.39 ± 1.43%; p = 0.19). CONCLUSIONS: T2*-CMR accurately quantified myocardial reperfusion hemorrhage in vivo. Hemorrhage was associated with more severe infarct-related injury.

Localization of spherical lesions in tumor-mimicking phantoms by 3D sparse array photoacoustic imaging.

PURPOSE: The authors have developed a sparse-array photoacoustic imaging (SPAI) system that is capable of mapping 3D distributions of optical absorption using a small number of laser pulses with no mechanical scanning needed. In previous studies, the authors have shown the localization accuracy and the high frame-rate image acquisition on simple phantoms with limited medical relevance. The purpose of this study was to test the imaging capabilities of SPAI in the context of breast tumor detection and localization. METHODS: The authors constructed an array of phantoms that include spherical lesions of sizes 1.5-9 mm, buried in highly scattering tissue phantoms at depths of 3-30 mm. The authors investigated both homogeneous lesions made of blood at varying concentrations and heterogeneous lesions containing vessel-like structures. Volumetric images of the deeply buried lesions were taken at increasingly shallower depths and image-based localization was compared to measured depth. RESULTS: The authors were able to detect and accurately localize homogeneous lesions having a realistic absorption coefficient of 0.2 cm(-1) down to depths of 9-20 mm, and heterogeneous lesions containing 0.5 mm diameter vessel-like structures down to depths of 13-20 mm. Image acquisition required 2.5 s for each volumetric lesion image. CONCLUSIONS: These results suggest that 3D SPAI can detect highly vascularized lesions well below 1 cm in diameter and can overcome optical scatter of tissue to depths of 1-2 cm. With further improvement in the sensitivity and noise characteristics of the imaging system, similar imaging depths should be within reach in real breast tissue. The method, due to its optical contrast, 3D imaging, and fast acquisition, may prove useful in the clinic as an adjunct to existing breast screening tools.

Development and characterization of an omnidirectional photoacoustic point source for calibration of a staring 3D photoacoustic imaging system.

Photoacoustic imaging is a modality which makes use of the contrast provided by optical imaging techniques and the spatial resolution and penetration depth similar to acoustic imaging modalities. We have developed a method for fast 3D photoacoustic imaging using a sparse hemispherical array of transducers. Such a system requires characterization of the transducer's response to an ideal point source in order to accurately reconstruct objects in the imaging volume. First, an attempt was made to design an ideal photoacoustic point source via a combination of liquids which would appropriately scatter and absorb the light such that a spherical distribution was achieved. Methylene blue (MB(+)) was used as the primary optical absorber while Intralipid (IL) was used as the liquid responsible for the optical scatter. A multitude of combinations were tested and the signal uniformity was characterized. The combination of 200 microM MB(+) and 0.09% IL was found to produce the most uniform signal over the range of transducers in the hemispherical array. The liquid source was then characterized over a broader range of azimuthal and zenith angles where it was shown the azimuthal consistency was much greater than the stability seen in different zenith elevations. The source was then used in a calibration scan for an imaging volume of 40 x 40 x 40 mm(3). At 216 points evenly spaced in the imaging volume, parameters were recorded for signal amplitude, width, and time-of-flight. These calibration parameters could then be applied to an iterative reconstruction algorithm in an attempt to more accurately produce images.

Depth of photothermal conversion of gold nanorods embedded in a tissue-like phantom.

Gold nanorod (AuNR)-assisted photothermal therapy has emerged as a viable method for selective killing of cancer cells and shows promise for tumor destruction in vivo. This study examined the distribution of AuNR conversion expected to occur during photothermal therapy in vivo. Tissue-like phantoms were prepared with polyethylene glycol AuNRs distributed homogeneously at a concentration representative of a systemic injection. Phantoms were illuminated with a nanosecond pulsed laser (800 nm) at a variety of combinations of pulse energy (12-120 mJ) and pulse count (1-1000). Operating at the American National Standards Institute safety limit for human skin exposure (30 mJ cm(-2)), a diameter of 13 mm and a depth of 7.6 mm of AuNR conversion were observed in the gel phantoms after 1000 laser pulses (100 s exposure). Significant AuNR conversion was measured to a depth of 6 mm after only 100 pulses. Comparison of the measured AuNR conversion distribution with Monte Carlo simulation suggested that the fluence threshold for AuNR conversion estimated from phantom measurements was in the range of 20-43 mJ cm(-2). The results suggest that AuNR-assisted photothermal therapy will be effective for tumors within 10 mm of the illuminated tissue surface.

Four-dimensional photoacoustic imaging of moving targets.

Photoacoustic imaging provides optical contrast with improved tissue penetration and spatial resolution compared to pure optical techniques. Three-dimensional photoacoustic imaging is particularly advantageous for visualizing non-planar light absorbing structures, such as blood vessels, internal organs or tumours. We have developed a fast 3-D photoacoustic imaging system for small animal research based on a sparse array of ultrasonic detectors and iterative image reconstruction. The system can acquire 3-D images with a single laser-shot at a frame rate of 10 Hz. To demonstrate the imaging capabilities we have constructed phantoms made of a scanning point source and a rotating line object and imaged them at a rate of 10 frames per second. The resulting 4-D photoacoustic images depicted well the motion of each target. Comparison of the perceived motion in the images with the known velocity of the target showed good agreement. To our knowledge, this is the first report of single-shot high frame-rate 3-D photoacoustic imaging system. With further developments, this system could bring to bear its inherent speed for applications in small animal research, such as motion tracking of tumour outline during respiration, and rapid monitoring of contrast agent kinetics.

Three-dimensional photoacoustic imaging by sparse-array detection and iterative image reconstruction.

Photoacoustic imaging (PAI) has the potential to acquire 3-D optical images at high speed. Attempts at 3-D photoacoustic imaging have used a dense 2-D array of ultrasound detectors or have densely scanned a single detector on a 2-D surface. The former approach is costly and complicated to realize, while the latter is inherently slow. We present a different approach based on a sparse 2-D array of detector elements and an iterative reconstruction algorithm. This approach has the potential for fast image acquisition, since no mechanical scanning is required, and for simple and compact construction due to the smaller number of detector elements. We obtained spatial sensitivity maps of the sparse array and used them to optimize the image reconstruction algorithm. We then validated the method on phantoms containing 3-D distributions of optically absorbing point sources. Reconstruction of the point sources from the time-domain signals resulted in images with good contrast and accurate localization (< or =1 mm error). Image acquisition time was 1 s. The results suggest that 3-D PAI with a sparse array of detector elements is a viable approach. Furthermore, the rapid acquisition speed indicates the possibility of high frame rate 3-D PAI.

Silver halide photonic crystal fibers for the middle infrared.

Photonic crystal fibers are normally holey silica fibers, which are opaque in the mid- and far-infrared. We have fabricated novel fibers by multiple extrusions of silver halide crystalline materials, which are highly transparent in the mid-infrared. These fibers are composed of two solid materials; The core consists of pure AgBr, and the cladding includes AgCl fiberoptic elements arranged in two concentric hexagonal rings around the core. Flexible fibers of outer diameter 1 mm and length of approximately 1 m were fabricated, and their optical properties were measured. These fibers exhibited core-clad behavior and would be extremely useful for IR laser power transmission, IR radiometry, and IR spectroscopy.