CHD1L: a new candidate gene for congenital anomalies of the kidneys and urinary tract (CAKUT)

Recently, we identified a microduplication in chromosomal band 1q21.1 encompassing the CHD1L/ALC1 gene encoding a chromatin-remodelling enzyme in congenital anomalies of the kidneys and urinary tract (CAKUT) patient.

Correlation between topographic N400 anomalies and reduced cerebral blood flow in the anterior temporal lobes of patients with dementia

In Alzheimer's disease (AD) patients, episodic memory impairments are apparent, yet semantic memory difficulties are also observed. While the episodic pathology has been thoroughly studied, the neurophysiological mechanisms of the semantic impairments remain obscure. Semantic dementia (SD) is characterized by isolated semantic memory deficits. The present study aimed to find an early marker of mild AD and SD by employing a semantic priming paradigm during electroencephalogram recordings. Event-related potentials (ERP) of early (P1, N1) and late (N400) word processing stages were obtained to measure semantic memory functions. Separately, baseline cerebral blood flow (CBF) was acquired with arterial spin labeling. Thus, the analysis focused on linear regressions of CBF with ERP topographical similarity indices in order to find the brain structures that showed altered baseline functionality associated with deviant ERPs. All participant groups showed semantic priming in their reaction times. Furthermore, decreased CBF in the temporal lobes was associated with abnormal N400 topography. No significant CBF clusters were found for the early ERPs. Taken together, the neurophysiological results suggested that the automatic spread of activation during semantic word processing was preserved in mild dementia, while controlled access to the words was impaired. These findings suggested that N400-topography alterations might be a potential marker for the detection of early dementia. Such a marker could be beneficial for differential diagnosis due to its low cost and non-invasive application as well as its relationship with semantic memory dysfunctions that are closely associated to the cortical deterioration in regions crucial for semantic word processing.

Important excess morbidity due to upper airway anomalies in the perioperative course in infant cardiac surgery

BACKGROUND: The study aimed at defining the excess morbidity or mortality caused by an additional airway malformation in children with congenital heart disease requiring surgery. METHODS: All patients requiring surgery for heart disease during an 8-year period ending in 2003 who had an associated upper airway malformation were retrospectively studied. All patients were seen in 2004 for a prospective follow-up examination. RESULTS: Eleven patients with upper airway anomalies were identified (tracheobronchial malacia in 6 patients, long-segment tracheal stenosis in 3, and bilateral vocal cord paralysis and tracheal hemangioma in 1 patient each). They accounted for 1.5% of the entire cardiac surgical load of 764 patients. In 5 infants, the airway anomaly was diagnosed before cardiac repair, in 6 patients thereafter. Diagnosis was made by bronchoscopy in all patients, by additional bronchography in 2. Failure of rapid postoperative extubation was the most common finding. Airway management was surgical in 2 and conservative in 8 patients, 1 newborn having been denied therapy because of the severity of airway hypoplasia. Compared with patients with isolated cardiac disease, those with additional airway anomalies had significantly longer duration of postoperative mechanical ventilation (median, 24 days versus 3), perioperative hospitalization (median, 72 days versus 11) and total number of days of hospitalization during the first year of life (median, 104 days versus 14). After a maximum follow-up of 8 years (median, 37 months) only 3 of 10 surviving patients remained symptomatic owing to the airway malformation. CONCLUSIONS: Upper airway anomalies accompanying heart disease in infancy resulted in a significant prolongation of perioperative intensive care and hospital stay, as well as duration of mechanical ventilation. Failure of early postoperative extubation was the leading symptom.

Longitudinal evaluation of cartilage composition of matrix-associated autologous chondrocyte transplants with 3-T delayed gadolinium-enhanced MRI of cartilage

OBJECTIVE: The purposes of this study were to use delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) to evaluate the zonal distribution of glycosaminoglycans (GAGs) in normal cartilage and repair tissue and to use 3-T MRI to monitor the GAG content in matrix-associated autologous chondrocyte transplants. SUBJECTS AND METHODS: Fifteen patients who underwent matrix-associated autologous chondrocyte transplantation in the knee joint underwent MRI at baseline and 3-T follow-up MRI 1 year later. Total and zonal changes in longitudinal relaxivity (deltaR1) and relative deltaR1 were calculated for repair tissue and normal hyaline cartilage and compared by use of analysis of variance. RESULTS: There was a significant difference between the mean deltaR1 of repair tissue and that of reference cartilage at baseline and follow-up (p < 0.001). There was a significant increase in deltaR1 value and a decrease in GAG content from the deep layer to the superficial layer in the reference cartilage and almost no variation and significantly higher values for the repair tissue at both examinations. At 1-year follow-up imaging, there was a 22.7% decrease in deltaR1 value in the deep zone of the transplant. CONCLUSION: T1 mapping with dGEMRIC at 3 T shows the zonal structure of normal hyaline cartilage, highly reduced zonal variations in repair tissue, and a tendency toward an increase in global and zonal GAG content 1 year after transplantation.

Differentiating normal hyaline cartilage from post-surgical repair tissue using fast gradient echo imaging in delayed gadolinium-enhanced MRI (dGEMRIC) at 3 Tesla

The purpose was to evaluate the relative glycosaminoglycan (GAG) content of repair tissue in patients after microfracturing (MFX) and matrix-associated autologous chondrocyte transplantation (MACT) of the knee joint with a dGEMRIC technique based on a newly developed short 3D-GRE sequence with two flip angle excitation pulses. Twenty patients treated with MFX or MACT (ten in each group) were enrolled. For comparability, patients from each group were matched by age (MFX: 37.1 +/- 16.3 years; MACT: 37.4 +/- 8.2 years) and postoperative interval (MFX: 33.0 +/- 17.3 months; MACT: 32.0 +/- 17.2 months). The Delta relaxation rate (DeltaR1) for repair tissue and normal hyaline cartilage and the relative DeltaR1 were calculated, and mean values were compared between both groups using an analysis of variance. The mean DeltaR1 for MFX was 1.07 +/- 0.34 versus 0.32 +/- 0.20 at the intact control site, and for MACT, 1.90 +/- 0.49 compared to 0.87 +/- 0.44, which resulted in a relative DeltaR1 of 3.39 for MFX and 2.18 for MACT. The difference between the cartilage repair groups was statistically significant. The new dGEMRIC technique based on dual flip angle excitation pulses showed higher GAG content in patients after MACT compared to MFX at the same postoperative interval and allowed reducing the data acquisition time to 4 min.

Comparison of delayed gadolinium enhanced MRI of cartilage (dGEMRIC) using inversion recovery and fast T1 mapping sequences

The delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) technique has shown promising results in pilot clinical studies of early osteoarthritis. Currently, its broader acceptance is limited by the long scan time and the need for postprocessing to calculate the T1 maps. A fast T1 mapping imaging technique based on two spoiled gradient echo images was implemented. In phantom studies, an appropriate flip angle combination optimized for center T1 of 756 to 955 ms yielded excellent agreement with T1 measured using the inversion recovery technique in the range of 200 to 900 ms, of interest in normal and diseased cartilage. In vivo validation was performed by serially imaging 26 hips using the inversion recovery and the Fast 2 angle T1 mapping techniques (center T1 756 ms). Excellent correlation with Pearson correlation coefficient R2 of 0.74 was seen and Bland-Altman plots demonstrated no systematic bias.

Direct MR arthrography at 1.5 and 3.0 T: signal dependence on gadolinium and iodine concentrations--phantom study

PURPOSE: To prospectively quantify in vitro the influence of gadopentetate dimeglumine and ioversol on the magnetic resonance (MR) imaging signal observed with a variety of musculoskeletal pulse sequences to predict optimum gadolinium concentrations for direct MR arthrography at 1.5 and 3.0 T. MATERIALS AND METHODS: In an in vitro study, T1 and T2 relaxation times of three dilution series of gadopentetate dimeglumine (concentration, 0-20.0 mmol gadolinium per liter) at ioversol concentrations with iodine concentration of 0, 236.4, and 1182 mmol iodine per liter (corresponding to 0, 30, and 150 mg of iodine per milliliter) were measured at 1.5 and 3.0 T. The relaxation rate dependence on concentrations of gadolinium and iodine was analytically modeled, and continuous profiles of signal versus gadolinium concentration were calculated for 10 pulse sequences used in current musculoskeletal imaging. After fitting to experimental discrete profiles, maximum signal-to-noise ratio (SNR), gadolinium concentration with maximum SNR, and range of gadolinium concentration with 90% of maximum SNR were derived. The overall influence of field strength and iodine concentration on these parameters was assessed by using t tests. The deviation of simulated from experimental signal-response profiles was assessed with the autocorrelation of the residuals. RESULTS: The model reproduced relaxation rates of 0.37-38.24 sec(-1), with a mean error of 4.5%. Calculated SNR profiles matched the discrete experimental profiles, with autocorrelation of the residuals divided by the mean of less than 5.0. Admixture of ioversol consistently reduced T1 and T2, narrowed optimum gadolinium concentration ranges (P = .004-.006), and reduced maximum SNR (P < .001 to not significant). Optimum gadolinium concentration was 0.7-3.4 mmol/L at both field strengths. At 3.0 T, maximum SNR was up to 75% higher than at 1.5 T. CONCLUSION: Admixture of ioversol to gadopentetate dimeglumine solutions results in a consistent additional relaxation enhancement, which can be analytically modeled to allow a near-quantitative a priori optimized match of contrast media concentrations and imaging protocol for a broad variety of pulse sequences.

Cartilage damage in femoroacetabular impingement (FAI): preliminary results on comparison of standard diagnostic vs delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC)

OBJECTIVES: To study the three-dimensional (3D) T1 patterns in different types of femoroacetabular impingement (FAI) by utilizing delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) and subsequent 3D T1 mapping. We used standard grading of OA by Tonnis grade on standard radiographs and morphological grading of cartilage in MRI for comparative analysis. METHODS: dGEMRIC was obtained from ten asymptomatic young-adult volunteers and 26 symptomatic FAI patients. MRI included the routine hip protocol and a dual-flip angle (FA) 3D gradient echo (GRE) sequence utilizing inline T1 measurement. Cartilage was morphologically classified from the radial images based on the extent of degeneration as: no degeneration, degeneration zone measuring <0.75 cm from the rim, >0.75 cm, or total loss. T1 findings were evaluated and correlated. RESULTS: All FAI types revealed remarkably lower T1 mean values in comparison to asymptomatic volunteers in all regions of interest. Distribution of the T1 dGEMRIC values was in accordance with the specific FAI damage pattern. In cam-types (n=6) there was a significant drop (P<0.05) of T1 in the anterior to superior location. In pincer-types (n=7), there was a generalized circumferential decrease noted. High inter-observer (intra-observer) reliability was noted for T1 assessment using intra-class correlation (ICC):intra-class coefficient=0.89 (0.95). CONCLUSIONS: We conclude that a pattern of zonal T1 variation does seem to exist that is unique for different sub-groups of FAI. The FA GRE approach to perform 3D T1 mapping has a promising role for further studies of standard MRI and dGEMRIC in the hip joint.

Delayed gadolinium-enhanced magnetic resonance imaging (dGEMRIC) of hip joint cartilage in femoroacetabular impingement (FAI): Are pre- and postcontrast imaging both necessary?

The purpose of this study was to assess if delayed gadolinium MRI of cartilage using postcontrast T(1) (T(1Gd)) is sufficient for evaluating cartilage damage in femoroacetabular impingement without using noncontrast values (T(10)). T(1Gd) and DeltaR(1) (1/T(1Gd) - 1/T(10)) that include noncontrast T(1) measurements were studied in two grades of osteoarthritis and in a control group of asymptomatic young-adult volunteers. Differences between T(1Gd) and DeltaR(1) values for femoroacetabular impingement patients and volunteers were compared. There was a very high correlation between T(1Gd) and DeltaR(1) in all study groups. In the study cohort with Tonnis grade 0, correlation (r) was -0.95 and -0.89 with Tonnis grade 1 and -0.88 in asymptomatic volunteers, being statistically significant (P < 0.001) for all groups. For both T(1Gd) and DeltaR(1), a statistically significant difference was noted between patients and control group. Significant difference was also noted for both T(1Gd) and DeltaR(1) between the patients with Tonnis grade 0 osteoarthritis and those with grade 1 changes. Our results prove a linear correlation between T(1Gd) and DeltaR(1), suggesting that T(1Gd) assessment is sufficient for the clinical utility of delayed gadolinium MRI of cartilage in this setting and additional time-consuming T(10) evaluation may not be needed.

Delayed gadolinium enhanced MRI of cartilage (dGEMRIC): Molekulare MRT-Bildgebung des Hüftgelenkknorpels [Delayed gadolinium enhanced MRI of cartilage (dGEMRIC): molecular MRI of hip joint cartilage]

Factors such as instability and impingement lead to early cartilage damage and osteoarthritis of the hip joint. The surgical outcome of joint-preserving surgery about the hip joint depends on the preoperative quality of joint cartilage.For in vivo evaluation of cartilage quality, different biochemically sensitive magnetic resonance imaging (MRI) procedures have been tested, some of which have the potential of inducing a paradigm shift in the evaluation and treatment of cartilage damage and early osteoarthritis.Instead of reacting to late sequelae in a palliative way, physicians could assess cartilage damage early on, and the treatment intensity could be adequate and based on the disease stage. Furthermore, the efficiency of different therapeutic interventions could be evaluated and monitored.This article reviews the recent application of delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and discusses its use for assessing cartilage quality in the hip joint. dGEMRIC is more sensitive to early cartilage changes in osteoarthritis than are radiographic measures and might be a helpful tool for assessing cartilage quality.