A layered single-side readout depth of interaction time-of-flight-PET detector.

We are exploring a scintillator-based PET detector with potential of high sensitivity, depth of interaction (DOI) capability, and timing resolution, with single-side readout. Our design combines two previous concepts: (1) multiple scintillator arrays stacked with relative offset, yielding inherent DOI information, but good timing performance has not been demonstrated with conventional light sharing readout. (2) Single crystal array with one-to-one coupling to the photodetector, showing superior timing performance compared to its light sharing counterparts, but lacks DOI. The combination, where the first layer of a staggered design is coupled one-to-one to a photodetector array, may provide both DOI and timing resolution and this concept is here evaluated through light transport simulations. Results show that: (1) unpolished crystal pixels in the staggered configuration yield better performance across all metrics compared to polished pixels, regardless of readout scheme. (2) One-to-one readout of the first layer allows for accurate DOI extraction using a single threshold. The number of multi pixel photon counter (MPPC) pixels with signal amplitudes exceeding the threshold corresponds to the interaction layer. This approach was not possible with conventional light sharing readout. (3) With a threshold of 2 optical photons, the layered approach with one-to-one coupled first layer improves timing close to the MPPC compared to the conventional one-to-one coupling non-DOI detector, due to effectively reduced crystal thickness. Single detector timing resolution values of 91, 127, 151 and 164 ps were observed per layer in the 4-layer design, to be compared to 148 ps for the single array with one-to-one coupling. (4) For the layered design with light sharing readout, timing improves with increased MPPC pixel size due to higher signal per channel. In conclusion, the combination of straightforward DOI determination, good timing performance, and relatively simple design makes the proposed concept promising for DOI-Time-of-Flight PET detectors.

Exploring light confinement in laser-processed LYSO:Ce for photon counting CT application.

With the goal of developing a low-cost scintillator-based photon counting detector (PCD) with high dose efficiency suitable for CT, the light transport characteristics in LYSO:Ce detectors containing laser induced optical barriers (LIOB) are simulated. Light confinement and light collection efficiencies (LCE) are studied for a variety of optical barrier patterns and properties (refractive index (RI) and barrier/crystal interface roughness). Up to 80% confinement is achievable with a simple pixel pattern with one barrier wall separating each pixel coupled one-to-one to a photodetector (PD) pixel. Confinement is heavily dependent on barrier properties, and rough interfaces and higher RI results in increased cross-talk. Three approaches to enhance performance beyond the basic pattern are explored: (1) Multiple barrier walls separating each crystal pixel. (2) Introduction of long and short range confinement by having multiple crystal pixels per PD pixel. (3) Combination of LIOB and laser ablation (LA). (1) Is effective for rough interfaces where confinement can be increased by up to 24% for double compared to single walls. (2) Results in high confinement in the pixel centered on the PD pixel, but lower confinement closer to the PD edge. This feature may be explored to achieve spatial resolution beyond the PD pixel size using light sharing based positioning algorithms. (3) Can increase confinement for smooth interfaces using a smooth ablation in the bottom part of the crystal. A general trend across all configurations is a trade-off between light confinement and LCE. The LCE attainable is found comparable to that for mechanically pixelated arrays. While the confinement achievable with LIOB is always lower compared to a mechanically pixelated array, the former may offer a high level of flexibility in terms of detector design. This, in combination with the possibility to fabricate sub-mm pixels in a cost-effective manner, makes LIOB a promising technology for scintillator-based PCDs.

Early developmental and allometric patterns in the electric yellow cichlid Labidochromis caeruleus.

The electric yellow cichlid Labidochromis caeruleus is a mouth-brooding haplochromine cichlid from Lake Malawi and one of the most popular cichlids in the ornamental fish industry. To investigate the early development of L. caeruleus from hatching until the juvenile stage, we studied its morphological development and allometric growth patterns. In newly-hatched larvae, most organs and body parts were not yet differentiated and continued to develop until 15 days post hatching (dph). The yolk sac was depleted at 13 dph. There was allometric growth, primarily in the anterior and posterior regions of the body, and inflection points when trajectories of allometric growth changed. Head and tail growth was prioritized, suggesting that body parts linked to feeding and swimming behaviour mature earlier than the rest of the body. Additionally, growth patterns revealed that development of organs related to vital functions such as branchial respiration, sensation, exogenous feeding and swimming was prioritized. Comparisons with other African and Neotropical cichlids revealed differences in ontogenetic processes and allometric growth along the anterior-posterior axis as well as variation in developmental timing. These results indicate how early morphological development and ontogenic processes might respond to the distinctive parental care observed in mouth-brooding cichlids.

Simulation study of light transport in laser-processed LYSO:Ce detectors with single-side readout.

A tightly focused pulsed laser beam can locally modify the crystal structure inside the bulk of a scintillator. The result is incorporation of so-called optical barriers with a refractive index different from that of the crystal bulk, that can be used to redirect the scintillation light and control the light spread in the detector. We here systematically study the scintillation light transport in detectors fabricated using the laser induced optical barrier technique, and objectively compare their potential performance characteristics with those of the two mainstream detector types: monolithic and mechanically pixelated arrays. Among countless optical barrier patterns, we explore barriers arranged in a pixel-like pattern extending all-the-way or half-way through a 20 mm thick LYSO:Ce crystal. We analyze the performance of the detectors coupled to MPPC arrays, in terms of light response functions, flood maps, line profiles, and light collection efficiency. Our results show that laser-processed detectors with both barrier patterns constitute a new detector category with a behavior between that of the two standard detector types. Results show that when the barrier-crystal interface is smooth, no DOI information can be obtained regardless of barrier refractive index (RI). However, with a rough barrier-crystal interface we can extract multiple levels of DOI. Lower barrier RI results in larger light confinement, leading to better transverse resolution. Furthermore we see that the laser-processed crystals have the potential to increase the light collection efficiency, which could lead to improved energy resolution and potentially better timing resolution due to higher signals. For a laser-processed detector with smooth barrier-crystal interfaces the light collection efficiency is simulated to >42%, and for rough interfaces >73%. The corresponding numbers for a monolithic crystal is 39% with polished surfaces, and 71% with rough surfaces, and for a mechanically pixelated array 35% with polished pixel surfaces and 59% with rough surfaces.

Novel laser-processed CsI:Tl detector for SPECT.

PURPOSE: The aim of this work is to demonstrate the feasibility of a novel technique for fabrication of high spatial resolution CsI:Tl scintillation detectors for single photon emission computed tomography systems. METHODS: The scintillators are fabricated using laser-induced optical barriers technique to create optical microstructures (or optical barriers) inside the CsI:Tl crystal bulk. The laser-processed CsI:Tl crystals are 3, 5, and 10 mm in thickness. In this work, the authors focus on the simplest pattern of optical barriers in that the barriers are created in the crystal bulk to form pixel-like patterns resembling mechanically pixelated scintillators. The monolithic CsI:Tl scintillator samples are fabricated with optical barrier patterns with 1.0 × 1.0 mm(2) and 0.625 × 0.625 mm(2) pixels. Experiments were conducted to characterize the fabricated arrays in terms of pixel separation and energy resolution. A 4 × 4 array of multipixel photon counter was used to collect the scintillation light in all the experiments. RESULTS: The process yield for fabricating the CsI:Tl arrays is 100% with processing time under 50 min. From the flood maps of the fabricated detectors exposed to 122 keV gammas, peak-to-valley (P/V) ratios of greater than 2.3 are calculated. The P/V values suggest that regardless of the crystal thickness, the pixels can be resolved. CONCLUSIONS: The results suggest that optical barriers can be considered as a robust alternative to mechanically pixelated arrays and can provide high spatial resolution while maintaining the sensitivity in a high-throughput and cost-effective manner.

Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling.

Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumours. Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumours of DLBCL patients, apparently reflecting the variation in tumour proliferation rate, host response and differentiation state of the tumour. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal centre B cells ('germinal centre B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'). Patients with germinal centre B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumours on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer.

Congenitally bicuspid aortic valves: a surgical pathology study of 542 cases (1991 through 1996) and a literature review of 2,715 additional cases.

OBJECTIVE: To describe a clinicopathologic study of a large group of congenitally bicuspid aortic valves surgically excised at a single institution. MATERIAL AND METHODS: The medical charts and bicuspid valves from patients undergoing aortic valve replacement at Mayo Clinic Rochester between 1991 and 1996 were retrospectively reviewed. RESULTS: The age of the 542 patients ranged from 1 to 86 years (mean, 61), and 372 (69%) were men. Among these, 409 (75%) had pure aortic stenosis (AS), 73 (13%) had pure aortic insufficiency (regurgitation) (AI), 53 (10%) had combined AS and AI, and 7 (1%) had normal function. The mean age was higher for those with AS than AI (65 versus 46 years; P < 0.001), whereas the male-to-female ratio was higher for AI than AS (17.3:1 versus 1.7:1; P < 0.001). The two cusps were not equal in size in 95%, and a raphe was present in 76% (67% typical, 9% atypical). Raphal position was described in 315 and was between the right and left cusps in 270 (86%). Raphal absence occurred more often in valves with equal-sized cusps than unequal (33% versus 14%; P = 0.005). Moderate to severe calcification affected valves with AS more frequently than AI (99% versus 41%; P < 0.001). In contrast, annular dilatation was associated with AI more than AS (48% versus 11%; P < 0.001). Acquired commissural fusion involved valves with combined AS and AI more often than the other functional states (31% versus 14%; P = 0.002). Sixteen patients (age range, 18 to 78 years; 13 men) had infective endocarditis (6 active, 10 healed), including 10 with AI (9 men), 3 with AS plus AI, 2 with AS, and 1 with normal function but embolization. CONCLUSION: Functionally, the most common fate of congenitally bicuspid aortic valves was calcific stenosis with or without regurgitation (85%). Because approximately 4 million US citizens have bicuspid valves and because valve replacement is currently the only treatment of symptomatic AS, this disorder will continue to affect health-care costs.

Radioiodinated (aminostyryl)pyridinium (ASP) dyes: new cell membrane probes for labeling mixed leukocytes and lymphocytes for diagnostic imaging.

We prepared [125I/131I]iodo-(aminostyryl)pyridinium dyes from tributylstannyl precursors. ASP 7a and 7b labeled leukocytes ex vivo (70-94%) using saline with or without washing plasma from cells. Viability of peripheral blood lymphocytes (PBLs) (dogs, rats) and splenic lymphocytes (rats) labeled with 7a and 7b (71-82%) was unchanged after labeling (> or = 88%). Canine 7b-leukocytes showed higher uptake in inflammatory lesions than did 111In-oxine leukocytes. At 3 h, aspirates contained more radioiodine than 111In (1.65:1 to 22:1) and radioiodine was cell bound. ROI measurements (3 h) gave abscess to contralateral knee ratios of 12.3 and 10.6 for 131I-7b vs. 4.8 and 2.3 for 111In-oxine.