Sub-millimeter precise photon interaction position determination in large monolithic scintillators via convolutional neural network algorithms.

In this work, we present the development and application of a convolutional neural network (CNN)-based algorithm to precisely determine the interaction position ofγ-quanta in large monolithic scintillators. Those are used as an absorber component of a Compton camera (CC) system under development for ion beam range verification via prompt-gamma imaging. We examined two scintillation crystals: LaBr3:Ce and CeBr3. Each crystal had dimensions of 50.8 mm × 50.8 mm × 30 mm and was coupled to a 64-fold segmented multi-anode photomultiplier tube (PMT) with an 8 × 8 pixel arrangement. We determined the spatial resolution for three photon energies of 662, 1.17 and 1.33 MeV obtained from 2D detector scans with tightly collimated137Cs and60Co photon sources. With the new algorithm we achieved a spatial resolution for the CeBr3 crystal below 1.11(8) mm and below 0.98(7) mm for the LaBr3:Ce detector for all investigated energies between 662 keV and 1.33 MeV. We thereby improved the performance by more than a factor of 2.5 compared to the previously used categorical average pattern algorithm, which is a variation of the well-established k-nearest neighbor algorithm. The trained CNN has a low memory footprint and enables the reconstruction of up to 104events per second with only one GPU. Those improvements are crucial on the way to future clinicalin vivoapplicability of the CC for ion beam range verification.

An HLA-DR11/DQ3 haplotype with a DRB1*0301 sequence motif in the third hypervariable region of the HLA-DR beta-1 chain: molecular and serological analysis of its generation in a European Caucasian family.

The formation of a new human leukocyte antigen (HLA)-DRB1 allele (DRB1*0340) has been detected during the routine testing of a European Caucasian blood and potential stem cell donor and his family. HLA typing of the donor with two polymerase chain reaction - sequence specific oligonucleotides (PCR-SSO) systems yielded inconclusive results. HLA typing of the family members including sequence-based typing of DRB1 in both directions after haplotype-specific amplification showed that the allele had most likely formed by a double crossover event in exon 2 of the DRB1 gene. The HLA haplotype containing the new allele was most probably derived from the father, who was typed as HLA-DRB1*0301,*1101 and DRB3*0101,*0202. The comparison of the sequences of the paternal DRB1 and DRB3 alleles with the exon 2 sequence of the DRB1*0340 showed that it had most likely formed through an uptake of at least the sequence part codons 58-77 of DRB1*0301 (donor) by DRB1*1101 (acceptor). We suppose that the recombination sites are located in the sequences from codons 38-57 and codons 78-88. At the protein level, more than 50% of the alpha-helical structure of the DRB1*1101 chain is replaced by a DRB1*0301-derived sequence with the exchange of several amino acids. Serological typing of the allele showed HLA-DR3. However, one monoclonal anti-DR11 of five DR11-reactive antibodies reacted positive, which might indicate residual immunogenic epitopes of DRB1*1101. HLA alleles that are most similar to HLA-DRB1*0340 are DRB1*030501, *0317, *0329 and *1107 with at least four amino acid differences in exon 2. In conclusion, HLA-DRB1*0340 is a new allele with unique properties compared with other known HLA-DRB alleles with regard to antigenicity, T-cell receptor-binding and peptide-binding possibilities.

Identification of the novel allele HLA-A*9237 in peripheral blood of a bone marrow donor.

The new HLA-A*9237 differs from HLA-A*020601 by one nonsynonymous nucleotide exchange at codon 127 (AAA to AAC).

Improved assessment of mitral valve stenosis by volumetric real-time three-dimensional echocardiography.

OBJECTIVES: This study was performed to determine the feasibility, accuracy and reproducibility of real-time volumetric three-dimensional echocardiography (3-D echo) for the estimation of mitral valve area in patients with mitral valve stenosis. BACKGROUND: Planimetry of the mitral valve area (MVA) by two-dimensional echocardiography (2-D echo) requires a favorable parasternal acoustic window and depends on operator skill. Transthoracic volumetric 3-D echo allows reconstruction of multiple 2-D planes in any desired orientation and is not limited to parasternal acquisition, and could thus enhance the accuracy and feasibility of calculating MVA. METHODS: In 48 patients with mitral stenosis (40 women; mean age 61 +/- 13 years) MVA was determined by planimetry using volumetric 3-D echo and compared with measurements obtained by 2-D echo and Doppler pressure half-time (PHT). All measurements were performed by two independent observers. Volumetric data were acquired from an apical view. RESULTS: Although 2-D echo allowed planimetry of the mitral valve in 43 of 48 patients (89%), calculation of the MVA was possible in all patients when 3-D echo was used. Mitral valve area by 3-D echo correlated well with MVA by 2-D echo (r = 0.93, mean difference, 0.09 +/- 0.14 cm2) and by PHT (r = 0.87, mean difference, 0.16 +/- 0.19 cm2). Interobserver variability was significantly less for 3-D echo than for 2-D echo (SD 0.08cm2 versus SD 0.23cm2, p < 0.001). Furthermore, it was much easier and faster to define the image plane with the smallest orifice area when 3-D echo was used. CONCLUSIONS: Transthoracic real-time volumetric 3-D echo provides accurate and highly reproducible measurements of mitral valve area and can easily be performed from an apical approach.

Congenital malformations of the right atrium and the coronary sinus: an analysis based on 103 cases reported in the literature and two additional cases.

STUDY OBJECTIVES: Congenital malformations of the right atrium (RA) and the coronary sinus (CS) are rare, and only sporadic cases have been reported. Little is known about the clinical relevance of this disorder. We report on two patients, one with a giant RA diverticulum, the other with a diverticulum of the CS, and review 103 cases of such malformations that have been reported previously. DESIGN: A MEDLINE search was performed to collect all cases of congenital malformations of the RA and the CS reported in the literature between 1955 and 1998. Cases were classified into the following categories: (1) congenital enlargement of the RA; (2) single diverticulum of the RA; (3) multiple diverticula of the RA; and (4) diverticulum of the CS. Clinical presentation and outcome of the different types of malformations were analyzed. RESULTS: The patients most frequently presenting with symptoms were those with diverticula of the CS (n = 28) followed by those with single diverticula of the RA (n = 13), multiple diverticula (n = 4), and congenital enlargements of the RA (n = 60). The percentages of symptomatic patients were 93, 84, 75, and 53%, respectively. Symptoms were frequently caused by arrhythmias. Supraventricular tachycardia (SVT) was found in 42 of the patients (40%) and was most common in patients with diverticula of the CS (24 of 28 patients) and multiple atrial diverticula (3 of 4 patients). Sudden cardiac death was reported more frequently in patients with diverticula of the CS (18%) compared to those with congenital enlargement of the RA (5%) or single or multiple diverticula of the RA (6%). All seven patients with diverticula of the CS who were not treated with catheter or surgical ablation eventually died. CONCLUSION: Congenital malformations of the RA and the CS frequently are associated with arrhythmias. SVT and sudden cardiac death have been reported in a significant percentage of patients with diverticula of the CS.

Stereolithographic biomodeling to create tangible hard copies of cardiac structures from echocardiographic data: in vitro and in vivo validation.

OBJECTIVES: This study investigated the feasibility, accuracy and clinical potential of creating polymer hard copies of echocardiographic data using stereolithography. BACKGROUND: Three-dimensional (3D) echocardiography has so far been limited by the need to display reconstructed 3D objects on a two-dimensional screen. Thus, tangible stereolithographic polymer models created from echocardiographic data could enhance our spatial perception of cardiac anatomy and pathology. METHODS: Hard-copy replicas of water-filled latex balloon phantoms (n = 7) and porcine liver specimens (n = 12) were generated from echocardiographic images using stereolithography (computerized laser polymerization). In addition, we created 24 models of the mitral valve from 12 transesophageal studies (normal = 6, mitral stenosis n = 4, prolapse/flail leaflet n = 8, annular dilation n = 2, leaflet restriction n = 2 and following mitral valve repair n = 2). RESULTS: Excellent agreement was found for comparison of volumes (r = 0.98, SEE = 3.46 mm3, mean difference = 0.25 +/- 3.33 mm3) and maximal dimensions (r = 0.99, SEE = 0.16 cm, mean difference = 0.03 +/- 0.16 cm) between phantoms and their corresponding replicas. Visual and tactile examination of mitral valve models by two blinded observers allowed correct depiction of mitral valve anatomy and pathology in all cases. CONCLUSIONS: Stereolithographic modeling of echocardiographic images is feasible and provides tangible polyacrylic models that are true to scale, shape and volume. Such models offer accurate depiction of mitral valve anatomy and pathology in patients studied with transesophageal echocardiography. This technique could have substantial impact on diagnosis, management and preoperative planning in complex cardiovascular disorders.

Comparison of perioperative myocardial protection with nifedipine versus nifedipine and metoprolol in patients undergoing elective coronary artery bypass grafting.

A randomized study was performed on 70 patients undergoing elective coronary bypass grafting to examine whether the combined infusion of the calcium channel blocker nifedipine (10 micrograms/kg per hour) and the beta 1-blocker metopropol (12 micrograms/kg per hour, n = 34) reduces the prevalence of perioperative myocardial ischemia and arrhythmias. The control group received nifedipine alone (n = 36). In both groups the infusion was started from the onset of extracorporal circulation and maintained over a period of 24 hours. Repeated 12-lead electrocardiographic and 3-channel Holter monitor recordings for 48 hours were used to define perioperative myocardial ischemia (transient ischemic event, myocardial infarction) and arrhythmias (sinus tachycardia, supraventricular tachycardia, atrial flutter/fibrillation, ventricular tachycardia). Hemodynamic parameters were repeatedly assessed for 24 hours and serum enzyme levels (creatine kinase, MB isoenzyme of creatine kinase) for up to 36 hours after the operation. The two groups did not differ significantly with respect to preoperative anamnestic and surgical data. No signs of perioperative myocardial infarction were detected in either group. However, a significantly lower incidence of transient ischemic episodes was observed in the nifedipine-metoprolol group than in the nifedipine group (3% vs 11%; p < 0.05). In addition, there was a tendency toward lower creatine kinase MB levels and peak values of creatine kinase and creatine kinase MB in the nifedipine-metoprolol group. With regard to perioperative arrhythmias, there was a significantly lower incidence of sinus tachycardia and atrial flutter/fibrillation in the nifedipine-metoprolol group (9% and 6%) than in the nifedipine group (33% and 27%, p < 0.05). In addition, postoperative heart rate was lower in the nifedipine-metoprolol group starting from the sixth hour after release of the aortic crossclamp (p < 0.05 and p < 0.01, respectively). No other hemodynamic parameters showed significant differences between the two groups and all returned to preoperative levels within 24 hours. In conclusion, perioperative application of nifedipine and metoprolol in patients undergoing elective coronary bypass grafting reduces the prevalence of perioperative myocardial ischemia and arrhythmias without significant negative inotropic effects. The combined infusion of the two drugs appears superior to nifedipine alone in preventing perioperative myocardial ischemia and reducing reperfusion-induced arrhythmias.

Combined perioperative infusion of nifedipine and metoprolol provides antiischemic and antiarrhythmic protection in patients undergoing elective aortocoronary bypass surgery.

A randomized study was performed on 70 patients undergoing elective coronary bypass surgery to examine whether the combined, perioperative, 24-hour infusion of the calcium-channel blocker nifedipine (10 micrograms/kg/h) and the beta 1-blocker metoprolol (12 micrograms/kg/h) reduces the incidence of perioperative myocardial ischemia and arrhythmias (group NM, n = 34). The control group received nifedipine only (n = 36). Repeated assessment of serum enzyme levels (CK, CK-MB) and 12-lead ECG, together with 3-channel Holter monitoring over 48 h were used to define perioperative myocardial ischemia (transient ischemic event, myocardial infarction) and supraventricular and ventricular arrhythmias. The two groups did not significantly differ with respect to preoperative anamnestic and surgical data. No perioperative myocardial infarction was detected in either group. However, a significantly lower incidence of transient ischemic events was observed in the NM group as compared to the nifedipine group (3% versus 11%; p < 0.05). In addition, there was a tendency towards lower CK-MB levels and peak-values of CK- and CK-MB in the NM group. With regard to perioperative dysrhythmias, there was a significantly lower incidence of sinus tachycardia (9%) and atrial flutter/fibrillation (6%) in the NM group as compared to the nifedipine group (33 and 27%, p < 0.05). In addition, postoperative heart rate was lower in the NM group starting from the 6th hour after opening of the aortic cross-clamp. In conclusion, the combined perioperative infusion of nifedipine and metoprolol is superior in preventing perioperative myocardial ischemia and decreasing the incidence of supraventricular arrhythmias as compared to a single-drug regimen with nifedipine.

Nifedipine reduces the incidence of myocardial infarction and transient ischemia in patients undergoing coronary bypass grafting.

A randomized study was performed on 104 patients undergoing elective coronary artery bypass grafting to examine whether the infusion of nifedipine (n = 53) reduces the incidence of perioperative myocardial ischemia and necrosis in the early postoperative period. Continuous hemodynamic and three-channel Holter monitoring was performed for 24 hours and serial assessment of serum enzymes and 12-lead electrocardiography were performed for 36 hours postoperatively. Nifedipine (minimum dose, 10 micrograms/kg/hr for 24 hours) was applied from the onset of extracorporal circulation. The control group (n = 51) received nitroglycerin (minimum dose, 1 micrograms/kg/min for 24 hours). Using the combined analyses of electrocardiography and Holter recordings, myocardial ischemia was defined as being either a transient ischemic event (TIE), transient coronary spasm (TCS), or myocardial infarction (MI). The two groups did not differ with respect to preoperative New York Heart Association classification, age, history of myocardial infarction, extracorporal circulation and aortic cross-clamp time, number of distal anastomoses, or systemic and pulmonary hemodynamics. The incidence of perioperative myocardial ischemia was substantially lower in the nifedipine than in the nitroglycerin group [TIE: three of 53 patients (6%) versus nine of 50 patients (18%), p less than 0.001; MI: two of 53 patients (4%) versus six of 50 patients (12%), p less than 0.001; and TCS: none of 53 patients (0%) versus two of 50 patients (4%), p = NS].(ABSTRACT TRUNCATED AT 250 WORDS)

Infusion of nifedipine after coronary artery bypass grafting decreases the incidence of early postoperative myocardial ischemia.

We performed a randomized study on patients undergoing elective coronary bypass grafting to examine whether postoperative infusion of nifedipine (n = 25) could reduce the incidence of isolated transient myocardial ischemia, myocardial infarction, or both. The control group (n = 25) received nitroglycerin. Hemodynamic and Holter monitoring and serial assessment of enzymatic and electrocardiographic changes were performed for all patients. Both groups showed comparable preoperative and operative data. The incidence of myocardial infarction was significantly lower in the nifedipine group (n = 1) as compared with the control group (n = 4), whereas the number of patients with isolated transient myocardial ischemia was similar in both groups (nifedipine, 3; control, 4). At the time of peak activity, levels of creatine kinase (350 +/- 129 versus 511 +/- 287 IU/mL), creatine kinase-MB (8.4 +/- 5.4 versus 17.1 +/- 11.0 IU/mL), and glutamate-oxaloacetate-transaminase (30.4 +/- 4.4 versus 41.0 +/- 7.9 IU/mL) were markedly lower in the nifedipine group (p less than 0.05). We conclude that infusion of nifedipine after elective coronary artery bypass grafting effectively decreases the incidence of myocardial infarction and the extent of myocardial necrosis during the early postoperative period.