Arterial spin-labeling MRI perfusion in tuberous sclerosis: correlation with PET

Neuroimaging using magnetic resonance imaging (MRI) is required for the investigation of surgically intractable epilepsy. In addition to the standard MRI techniques, perfusion sequences can be added to improve visualization of the underlying pathological changes. Also, as arterial spin-labeling (ASL) MRI perfusion does not require contrast administration, it may even be advantageous in these patients. We report here on three patients with epilepsy and tuberous sclerosis who underwent brain MRI with ASL and positron emission tomography (PET), both of which were found to correlate with each other and with electrophysiological data.

Thrombus imaging in acute stroke: correlation of thrombus length on susceptibility-weighted imaging with endovascular reperfusion success

OBJECTIVES Susceptibility-weighted imaging (SWI) enables visualization of thrombotic material in acute ischemic stroke. We aimed to validate the accuracy of thrombus depiction on SWI compared to time-of-flight MRA (TOF-MRA), first-pass gadolinium-enhanced MRA (GE-MRA) and digital subtraction angiography (DSA). Furthermore, we analysed the impact of thrombus length on reperfusion success with endovascular therapy. METHODS Consecutive patients with acute ischemic stroke due to middle cerebral artery (MCA) occlusions undergoing endovascular recanalization were screened. Only patients with a pretreatment SWI were included. Thrombus visibility and location on SWI were compared to those on TOF-MRA, GE-MRA and DSA. The association between thrombus length on SWI and reperfusion success was studied. RESULTS Eighty-four of the 88 patients included (95.5 %) showed an MCA thrombus on SWI. Strong correlations between thrombus location on SWI and that on TOF-MRA (Pearson's correlation coefficient 0.918, P < 0.001), GE-MRA (0.887, P < 0.001) and DSA (0.841, P < 0.001) were observed. Successful reperfusion was not significantly related to thrombus length on SWI (P = 0.153; binary logistic regression). CONCLUSIONS In MCA occlusion thrombus location as seen on SWI correlates well with angiographic findings. In contrast to intravenous thrombolysis, thrombus length appears to have no impact on reperfusion success of endovascular therapy. KEY POINTS • SWI helps in assessing location and length of thrombi in the MCA • SWI, MRA and DSA are equivalent in detecting the MCA occlusion site • SWI is superior in identifying the distal end of the thrombus • Stent retrievers should be deployed over the distal thrombus end • Thrombus length did not affect success of endovascular reperfusion guided by SWI.

Transient rhythmic network activity in the somatosensory cortex evoked by distributed input in vitro

The initiation and maintenance of physiological and pathophysiological oscillatory activity depends on the synaptic interactions within neuronal networks. We studied the mechanisms underlying evoked transient network oscillation in acute slices of the adolescent rat somatosensory cortex and modeled its underpinning mechanisms. Oscillations were evoked by brief spatially distributed noisy extracellular stimulation, delivered via bipolar electrodes. Evoked transient network oscillation was detected with multi-neuron patch-clamp recordings under different pharmacological conditions. The observed oscillations are in the frequency range of 2-5 Hz and consist of 4-12 mV large, 40-150 ms wide compound synaptic events with rare overlying action potentials. This evoked transient network oscillation is only weakly expressed in the somatosensory cortex and requires increased [K+]o of 6.25 mM and decreased [Ca2+]o of 1.5 mM and [Mg2+]o of 0.5 mM. A peak in the cross-correlation among membrane potential in layers II/III, IV and V neurons reflects the underlying network-driven basis of the evoked transient network oscillation. The initiation of the evoked transient network oscillation is accompanied by an increased [K+]o and can be prevented by the K+ channel blocker quinidine. In addition, a shift of the chloride reversal potential takes place during stimulation, resulting in a depolarizing type A GABA (GABAA) receptor response. Blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionate (AMPA), N-methyl-D-aspartate (NMDA), or GABA(A) receptors as well as gap junctions prevents evoked transient network oscillation while a reduction of AMPA or GABA(A) receptor desensitization increases its duration and amplitude. The apparent reversal potential of -27 mV of the evoked transient network oscillation, its pharmacological profile, as well as the modeling results suggest a mixed contribution of glutamatergic, excitatory GABAergic, and gap junctional conductances in initiation and maintenance of this oscillatory activity. With these properties, evoked transient network oscillation resembles epileptic afterdischarges more than any other form of physiological or pathophysiological neocortical oscillatory activity.

Morphological integration between the cranial base and the face in children and adults

The primary aim of the present study was to assess morphological covariation between the face and the basicranium (midline and lateral), and to evaluate patterns of integration at two specific developmental stages. A group of 71 children (6-10 years) was compared with a group of 71 adults (20-35 years). Lateral cephalometric radiographs were digitized and a total of 28 landmarks were placed on three areas; the midline cranial base, the lateral cranial base and the face. Geometric morphometric methods were applied and partial least squares analysis was used to evaluate correlation between the three shape blocks. Morphological integration was tested both with and without removing the effect of allometry. In children, mainly the midline and, to a lesser extent, the lateral cranial base were moderately correlated to the face. In adults, the correlation between the face and the midline cranial base, which ceases development earlier than the lateral base, was reduced. However, the lateral cranial base retained and even strengthened its correlation to the face. This suggests that the duration of common developmental timing is an important factor that influences integration between craniofacial structures. However, despite the apparent switch of primary roles between the cranial bases during development, the patterns of integration remained stable, thereby supporting the role of genetics over function in the establishment and development of craniofacial shape.

Evaluation of chronic HCV infection in transplanted livers using a modified histological activity index

The majority of histopathological classifications of primary chronic viral hepatitis and recurrence of HCV infection in liver transplants is based on the histological activity index (HAI) introduced by Knodell et al in 1981; however, correlation between HAI and clinical/laboratory data is poor. Therefore, the aim of this study was to present a modification of HAI (mHAI) adapted to distinct features of graft infection, and to evaluate its usefulness in the description of disease activity.

Detecting and resolving position-dependent temperature effects in real-time quantitative polymerase chain reaction

Real-time quantitative polymerase chain reaction (qPCR) depends on precise temperature control of the sample during cycling. In the current study, we investigated how temperature variation in plate-based qPCR instruments influences qPCR results. Temperature variation was measured by amplicon melting analysis as a convenient means to assess well-to-well differences. Multiple technical replicates of several SYBR Green I-based qPCR assays allowed correlation of relative well temperature to quantification cycle. We found that inadequate template denaturation results in an inverse correlation and requires increasing the denaturation temperature, adding a DNA destabilizing agent, or pretreating with a restriction enzyme. In contrast, inadequate primer annealing results in a direct correlation and requires lowering the annealing temperature. Significant correlations were found in 18 of 25 assays. The critical nature of temperature-dependent effects was shown in a blinded study of 29 patients for the diagnosis of Prader-Willy and Angelman syndromes, where eight diagnoses were incorrect unless temperature-dependent effects were controlled. A method to detect temperature-dependent effects by pairwise comparisons of replicates in routine experiments is presented and applied. Systematic temperature errors in qPCR instruments can be recognized and their effects eliminated when high precision is required in quantitative genetic diagnostics and critical complementary DNA analyses.

Contrast-enhanced 3-D MRA in decision making for carotid endarterectomy: a 6-year experience

BACKGROUND: Systematic need for angiography in diagnosis of carotid artery stenosis and indication of surgical therapy is still debated. Noninvasive imaging techniques such as MR angiography (MRA) or CT angiography (CTA) offer an alternative to digital subtraction angiography (DSA) and are increasingly used in clinical practice. In this study, we present the radiological characteristics and clinical results of a series of patients operated on the basis of combined ultrasonography (US)/MRA. METHODS: This observational study included all the patients consecutively operated for a carotid stenosis in our Department from October 1998 to December 2004. The applied MRA protocol had previously been established in a large correlation study with DSA. DSA was used only in case of discordance between US and MRA. The preoperative radiological information furnished by MRA was compared with intraoperative findings. The outcome of the operation was assessed according to ECST criteria. RESULTS: Among 327 patients, preoperative MRA was performed in 278 (85%), DSA in 44 (13.5%) and CT angiography in 5 (1.5%). Most of DSA studies were performed as emergency for preparation of endovascular therapy or for reasons other than carotid stenosis. Eleven additional DSA (3.3%) complemented US/MRA, mostly because diverging diagnosis of subocclusion of ICA. No direct morbidity or intraoperative difficulty was related to preoperative MRA. Combined mortality/major morbidity rate was 0.9% (3 patients) and minor morbidity rate 5.5% (18 patients). CONCLUSIONS: This observational study describes a well-established practice of carotid surgery and supports the exclusive use of non invasive diagnostic imaging for indicating and deciding the operation.

Histomorphologic evaluation of extracorporeal shock wave therapy of the fourth metatarsal bone and the origin of the suspensory ligament in horses without lameness

OBJECTIVE: To determine via histologic examination and scintigraphy the effect of focused extracorporeal shock wave therapy (ESWT) on normal bone and the bone-ligament interface in horses. ANIMALS: 6 horses without lameness. PROCEDURE: Origins of the suspensory ligament at the metacarpus (35-mm probe depth) and fourth metatarsal bone (5-mm probe depth) were treated twice (days 0 and 16) with 2,000 shocks (energy flux density, 0.15 mJ/mm2). One forelimb and 1 hind limb were randomly treated, and the contralateral limbs served as nontreated controls. Bone scans were performed on days -1 (before ESWT), 3, 16, and 19. Histomorphologic studies of control and treated tissues were performed on day 30. RESULTS: ESWT significantly increased the number of osteoblasts but caused no damage to associated soft tissue structures and did not induce cortical microfractures. A significant correlation between osteoblast numbers and radiopharmaceutical uptake was noticed on lateral views of the hind limb on days 3 and 16 and on caudal views of the forelimb on day 3. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that ESWT has the potential to increase osteoblast numbers in horses. The correlation between increased osteoblast numbers and radio-pharmaceutical uptake 3 days and 16 days after the first ESWT suggested that stimulation of osteogenesis occurred soon after ESWT. No damage to bone or the bone-ligament interface should occur at the settings used in this study, and ESWT can therefore be administered safely in horses.

Deadspace estimation from CO2 versus molar mass measurements in infants

BACKGROUND: Estimation of respiratory deadspace is often based on the CO2 expirogram, however presence of the CO2 sensor increases equipment deadspace, which in turn influences breathing pattern and calculation of lung volume. In addition, it is necessary to correct for the delay between the sensor and flow signals. We propose a new method for estimation of effective deadspace using the molar mass (MM) signal from an ultrasonic flowmeter device, which does not require delay correction. We hypothesize that this estimation is correlated with that calculated from the CO2 signal using the Fowler method. METHODS: Breath-by-breath CO2, MM and flow measurements were made in a group of 77 term-born healthy infants. Fowler deadspace (Vd,Fowler) was calculated after correcting for the flow-dependent delay in the CO2 signal. Deadspace estimated from the MM signal (Vd,MM) was defined as the volume passing through the flowhead between start of expiration and the 10% rise point in MM. RESULTS: Correlation (r = 0.456, P < 0.0001) was found between Vd,MM and Vd,Fowler averaged over all measurements, with a mean difference of -1.4% (95% CI -4.1 to 1.3%). Vd,MM ranged from 6.6 to 11.4 ml between subjects, while Vd,Fowler ranged from 5.9 to 12.0 ml. Mean intra-measurement CV over 5-10 breaths was 7.8 +/- 5.6% for Vd,MM and 7.8 +/- 3.7% for Vd,Fowler. Mean intra-subject CV was 6.0 +/- 4.5% for Vd,MM and 8.3 +/- 5.9% for Vd,Fowler. Correcting for the CO2 signal delay resulted in a 12% difference (P = 0.022) in Vd,Fowler. Vd,MM could be obtained more frequently than Vd,Fowler in infants with CLD, with a high variability. CONCLUSIONS: Use of the MM signal provides a feasible estimate of Fowler deadspace without introducing additional equipment deadspace. The simple calculation without need for delay correction makes individual adjustment for deadspace in FRC measurements possible. This is especially important given the relative large range of deadspace seen in this homogeneous group of infants.

Coronary artery stent geometry and in-stent contrast attenuation with 64-slice computed tomography

We aimed at assessing stent geometry and in-stent contrast attenuation with 64-slice CT in patients with various coronary stents. Twenty-nine patients (mean age 60 +/- 11 years; 24 men) with 50 stents underwent CT within 2 weeks after stent placement. Mean in-stent luminal diameter and reference vessel diameter proximal and distal to the stent were assessed with CT, and compared to quantitative coronary angiography (QCA). Stent length was also compared to the manufacturer's values. Images were reconstructed using a medium-smooth (B30f) and sharp (B46f) kernel. All 50 stents could be visualized with CT. Mean in-stent luminal diameter was systematically underestimated with CT compared to QCA (1.60 +/- 0.39 mm versus 2.49 +/- 0.45 mm; P < 0.0001), resulting in a modest correlation of QCA versus CT (r = 0.49; P < 0.0001). Stent length as given by the manufacturer was 18.2 +/- 6.2 mm, correlating well with CT (18.5 +/- 5.7 mm; r = 0.95; P < 0.0001) and QCA (17.4 +/- 5.6 mm; r = 0.87; P < 0.0001). Proximal and distal reference vessel diameters were similar with CT and QCA (P = 0.06 and P = 0.03). B46f kernel images showed higher image noise (P < 0.05) and lower in-stent CT attenuation values (P < 0.001) than images reconstructed with the B30f kernel. 64-slice CT allows measurement of coronary artery in-stent density, and significantly underestimates the true in-stent diameter compared to QCA.

Quality of life and coping behaviour in Type 1 diabetes mellitus: relationship with metabolic control

Uncovering factors possibly leading to insufficient metabolic control in Type 1 diabetes, both on the part of the patient or the treating physician, is of considerable relevance. The present long-term study investigated the relevance of patient-related vs education-related factors for the success in achieving acceptable glycaemic control. Adolescents or young adults with Type 1 diabetes mellitus (n= 26, mean age= 22+/-2 yr, diabetes duration= 11+/-5 yr) were followed during 36+/-5 months. All patients were treated by the same diabetologist. At the beginning of the study coping behaviour, quality of life and evaluation of emotional status were assessed. Changes in HbA1c were used as a parameter of glycaemic control. At follow-up there was a significant decrease in HbA1c of 0.4% (p<0.01). However, this was not in statistically significant correlation with age, gender, aspects of quality of life or coping behaviour. Therefore, glycaemic control and/or improvement of glycaemic control in adolescents or young adults with Type 1 diabetes mellitus seems to be primarily related to other factors, eg continuous education provided in a stable setting.

Formal speech stylistics and type A behavior in 38 subjects during nonstress interviews

Open-ended interviews of 90 min length of 38 patients were analyzed with respect to speech stylistics, shown by Schucker and Jacobs to differentiate individuals with type A personality features from those with type B. In our patients, Type A/B had been assessed by the Bortner Personality Inventory. The stylistics studied were: repeated words swallowed words, interruptions, simultaneous speech, silence latency (between question and answer) (SL), speed of speech, uneven speed of speech (USS), explosive words (PW), uneven speech volume (USV), and speech volume. Correlations between both raters for all speech categories were high. Positive correlations between extent of type A and SL (r = 0.33; p = 0.022), USS (r = 0.51; p = 0.002), PW (r = 0.46; p = 0.003) and USV (r = 0.39; p = 0.012) were found. Our results indicate that the speech in nonstress open-ended interviews of type A individuals tends to show a higher emotional tension (positive correlations for USS PW and USV) and is more controlled in conversation (positive correlation for SL).

Inverse thermodilution with conventional pulmonary artery catheters for the assessment of cerebral, hepatic, renal, and femoral blood flow

Assessment of regional blood flow changes is difficult in the clinical setting. We tested whether conventional pulmonary artery catheters (PACs) can be used to measure regional venous blood flows by inverse thermodilution (ITD). Inverse thermodilution was tested in vitro and in vivo using perivascular ultrasound Doppler (USD) flow probes as a reference. In anesthetized pigs, PACs were inserted in jugular, hepatic, renal, and femoral veins, and their measurements were compared with simultaneous USD flow measurements from carotid, hepatic, renal, and femoral arteries and from portal vein. Fluid boluses were injected through the PAC's distal port, and temperature changes were recorded from the proximally located thermistor. Injectates of 2 and 5 mL at 22 degrees C and 4 degrees C were used. Flows were altered by using a roller pump (in vitro), and infusion of dobutamine and induction of cardiac tamponade, respectively. In vitro: At blood flows between 400 mL . min-1 and 700 mL . min-1 (n = 50), ITD and USD correlated well (r = 0.86, P < 0.0001), with bias and limits of agreement of 3 +/- 101 mL . min-1. In vivo: 514 pairs of measurements had to be excluded from analysis for technical reasons, and 976 were analyzed. Best correlations were r = 0.87 (P < 0.0001) for renal flow and r = 0.46 (P < 0.0001) for hepatic flow. No significant correlation was found for cerebral and femoral flows. Inverse thermodilution using conventional PAC compared moderately well with USD for renal but not for other flows despite good in vitro correlation in various conditions. In addition, this method has significant technical limitations.

Dynamic contour tonometry in keratoconus and postkeratoplasty eyes

PURPOSE: To compare the performance of dynamic contour tonometry (DCT) and Goldmann applanation tonometry (GAT) in measuring intraocular pressure in eyes with irregular corneas. METHODS: GAT and DCT measures were taken in 30 keratoconus and 29 postkeratoplasty eyes of 35 patients after pachymetry and corneal topography. Regression and correlation analyses were performed between both tonometry methods and between tonometry methods and corneal parameters. Bland-Altman plots were constructed. RESULTS: DCT values were significantly higher than GAT values in both study groups: +4.1 +/- 2.3 mm Hg (mean +/- SD) in keratoconus and +3.1 +/- 2.5 mm Hg after keratoplasty. In contrast to DCT, GAT values were significantly higher in postkeratoplasty eyes than in keratoconus. The correlation between the 2 tonometry methods was moderate in keratoconus (Kendall correlation coefficient, tau = 0.34) as well in postkeratoplasty eyes (tau = 0.66). The +/-1.96 SD span of the DCT-GAT differences showed a considerable range: -0.42 to +8.70 mm Hg in keratoconus and -1.87 to +7.98 mm Hg in postkeratoplasty eyes. In the keratoconus group, neither DCT nor GAT correlated significantly with any of the corneal parameters. In the postkeratoplasty group, both DCT and GAT measures showed a moderate positive correlation with corneal steepness, but only DCT had a significant negative correlation with the central corneal thickness (tau = -0.33). CONCLUSIONS: DCT measured significantly higher intraocular pressures than GAT in keratoconus and postkeratoplasty eyes. DCT and GAT measures varied considerably, and DCT was not less dependent on biomechanical properties of irregular corneas than GAT.