T2 mapping with magnetization‐prepared 3D TSE based on a modified BIR‐4 T2 preparation

The purpose of this work was to investigate the performance of the modified BIR‐4 T₂ preparation for T₂ mapping and propose a method to remove T₂ quantification errors in the presence of large B₁ and B₀ offsets. The theoretical investigation of the magnetization evolution during the T₂ preparation in the presence of B₁ and B₀ offsets showed deviations from a mono‐exponential T₂ decay (two parameter fit). A three parameter fit was used to improve T₂ accuracy. Furthermore, a two parameter fit with an additional saturation preparation scan was proposed to improve T₂ accuracy and precision. These three fitting methods were compared based on simulations, phantom measurements and an in vivo healthy volunteer study of the neck musculature using a 3D TSE readout. The results based upon the pure two parameter fit overestimated T₂ in regions with high B₀ offsets (up to 40% in phantoms). The three parameter fit T₂ values were robust to B₀ offsets but with higher standard deviation (up to 40% in simulations). The two parameter fit with the saturation preparation yielded high robustness towards B₀ offsets with a noise performance comparable to that of the two parameter fit. In the volunteer study the T₂ values obtained by the pure two parameter fit showed a dependence on the field inhomogeneities, whereas the T₂ values from the proposed fitting approach were shown to be insensitive to B₀ offsets. The proposed method enabled accurate and precise T₂ mapping in the presence of large B₁ and B₀ offsets.     

Cystic fibrosis transmembrane conductance regulator mutations in azoospermic and oligospermic men and their partners

The objective of this study was to investigate the contribution of cystic fibrosis transmembrane conductance regulator (CFTR) to human infertility and to define screening and counselling procedures for couples asking for assisted reproduction treatment. Extended CFTR mutation screening was performed in 310 infertile men (25 with congenital absence of the vas deferens (CAVD), 116 with non-CAVD azoospermia, 169 with severe oligospermia), 70 female partners and 96 healthy controls. CFTR mutations were detected in the majority (68%) of CAVD patients and in significant proportions in azoospermic (31%) and oligospermic (22%) men. Carrier frequency among partners of infertile men was 16/70, exceeding that of controls (6/96) significantly (P = 0.0005). Thus, in 23% of infertile couples both partners were carriers, increasing the risk for their offspring to inherit two mutations to 25% or 50%. This study emphasizes the necessity to offer extended CFTR mutation screening and counselling not only to patients with CAVD but also to azoospermic and oligozoospermic men and their partners before undergoing assisted reproduction techniques. The identification of rare and/or mild mutations will not be a reason to abstain from parenthood, but will allow adequate treatment in children at risk for atypical or mild cystic fibrosis as soon as they develop any symptoms.     

Frequency-domain analysis of fast oddball responses to visual stimuli: A feasibility study

Event-related potential responses to oddball stimuli, including the P300 component, have been proposed as a diagnostic tool for discerning psychiatric or higher-level neural disorders from malingering, for instance in cases of unexplained visual loss. For clinical use, short recording durations and easy statistical assessment are highly desirable. With this aim, we investigated the feasibility of recording oddball responses in a fast steady-state regime. We used gratings with two possible orientations in a rapid oddball paradigm with an inter-stimulus interval of 214 ms. Six consecutive presentations of one stimulus type (frequent) were followed by a single presentation of the other (infrequent) stimulus type. Subjects were attending to the rare stimulus type. The electroencephalographic recordings were analyzed in the frequency domain. All subjects produced significant harmonic responses related to the processing of the rare stimulus, demonstrating the feasibility of the technique, with the potential of reducing recording times substantially compared to conventional slow stimulation. We furthermore found that the regularity of the occurrence of infrequent stimuli, which is necessary for frequency-domain analysis, does not per se reduce the P300 responses, as would have been expected in the framework of some hypotheses regarding the role of the P300.     

Immune reconstitution after haematopoietic cell transplantation in children: immunophenotype analysis with regard to factors affecting the speed of recovery

Immune reconstitution was studied prospectively in 66 children who underwent 77 haematopoietic cell transplantations (HCT): 46 autologous HCTs in 39 patients and 31 allogeneic HCTs in 27 patients. We studied the dynamic analysis of immune recovery with regard to potential factors affecting its speed, including age, type of HCT, diagnosis, graft-versus-host disease (GvHD) and cytomegalovirus (CMV) infection reactivation. Absolute counts of different lymphocyte subsets and immunoglobulin serum levels were determined in peripheral blood of patients on d -7 and +16, and then at various intervals up to 24 months post transplant. Common patterns of immune recovery after both allogeneic and autologous HCT were identified: (i) CD4+CD45RO+ peripheral T-cell expansion on d +16; (ii) inverted CD4+:CD8+ ratio from d +30 onwards; (iii) rapid natural killer (NK) cell (CD16+/-CD56+) count normalization. We observed prolonged T-cell lymphopenia (CD3+, CD3+CD4+, CD4+CD45RA+) until 24 months after autologous HCT, whereas in the allogeneic setting CD3+CD4+ cells, including naive CD45RA+ cells, returned to normal values at 9 months post transplant. Age > 10 years and coexistence of GvHD and CMV reactivation were associated with a substantial delay in T- (CD4+, including CD45RA+) and B-cell recovery after allogeneic HCT. Multidrug GvHD prophylaxis resulted in impaired T- (CD4+, CD4+CD45RA+) and B-cell reconstitution only in the early phase after allogeneic HCT (up to 4 months). Our results demonstrated that T-cell recovery was severely impaired in children after autologous HCT. It should be emphasized that specific approaches to enhance immune reconstitution are necessary to control minimal residual disease and avoid the risk of infectious complications in the autologous setting. Thymic involution after allogeneic HCT seems to be associated with age and coexistence of GvHD and CMV reactivation.