Leonard J. van Schelven

MRI-guided robotic system for transperineal prostate interventions: proof of principle

In this study, we demonstrate the proof of principle of the University Medical Center Utrecht (UMCU) robot dedicated to magnetic resonance imaging (MRI)-guided interventions in patients. The UMCU robot consists of polymers and non-ferromagnetic materials. For transperineal prostate interventions, it can be placed between the patients legs inside a closed bore 1.5T MR scanner. The robot can manually be translated and rotated resulting in five degrees of freedom. It contains a pneumatically driven tapping device to automatically insert a needle stepwise into the prostate using a controller unit outside the scanning room. To define the target positions and to verify the needle insertion point and the needle trajectory, a high-resolution 3D balanced steady state free precession (bSSFP) scan that provides a T2/T1-weighted contrast is acquired. During the needle insertion fast 2D bSSFP images are generated to track the needle on-line. When the target position is reached, the radiation oncologist manually places a fiducial gold marker (small seed) at this location. In total two needle trajectories are used to place all markers. Afterwards, a high-resolution 3D bSSFP scan is acquired to visualize the fiducial gold markers. Four fiducial gold markers were placed transperineally into the prostate of a patient with a clinical stage T3 prostate cancer. In the generated scans, it was possible to discriminate the patients anatomy, the needle and the markers. All markers were delivered inside the prostate. The procedure time was 1.5 h. This study proves that MRI-guided needle placement and seed delivery in the prostate with the UMCU robot are feasible.

Subtle involvement of the parasympathetic nervous system in patients with irritable bowel syndrome

This study comprises assessment of autonomic function in irritable bowel syndrome (IBS) patients, focusing on meal-related changes. In 18 IBS patients (4 males, mean age 45±3.0 [SEM] years) and 19 healthy volunteers (6 males, mean age 41±3.5 years) blood pressure, heart rate, heart rate variability and muscle sympathetic nerve activity (MSNA) were assessed before, during and after consumption of a standardized meal. In pre- and postprandial phase Valsalva maneuver, cold pressor test (CPT) and deep breathing test were carried out and Visual Analog Scale (VAS) scores for nausea, bloating and pain were obtained.In the IBS group, the meal induced significantly higher VAS scores for pain (P=0.002) and bloating (P=0.02). During food intake, the increase in blood pressure, heart rate and MSNA was equal in patients and controls, but the increase of LF/HF ratio of heart rate variability was significantly higher in the IBS group (median [quartiles] 2.29 [1.14–3.00] versus 0.77 [0.25–1.81]; P=0.03). IBS patients scored lower on pre- and postprandial RRmax/RRmin ratio during deep breathing (DB ratio, P=0.03). The increase in MSNA (burst frequency) in response to CPT tended to be higher in the IBS patients (P=0.07). We conclude that reactivity to food intake, measured as muscle sympathetic nerve activity, is normal in IBS patients. The lower DB ratio and higher LF/HF ratio during food intake in IBS patients is an indication of a reduced parasympathetic reactivity. These results suggest that reduced baseline activity as well as responsiveness of the parasympathetic system could play a role in the pathogenesis of IBS.

Sodium profiling, but not cool dialysate, increases the absolute plasma refill rate during hemodialysis.

Intradialytic hypotension is often caused by a discrepancy between ultrafiltration and plasma refilling. Increasing the plasma refill rate could therefore reduce intradialytic hypotension. We used a recently developed method to measure the effect of cool dialysate and sodium (Na) profiling on refill during hemodialysis (HD). Using a Gambro AK200 with blood volume (BV) sensor plus computer-guided external pump, a high ultrafiltration rate quickly induced a preset BV reduction. A software feedback mechanism subsequently adjusted the ultrafiltration rate continuously to maintain BV between very narrow preset boundaries. The continuously changing, software-generated ultrafiltration rate then quantitatively equalled refill. Absolute plasma refill rate was measured in six stable patients without intradialytic hypotension, undergoing HD without intervention, with cool dialysate (1°C below core temperature), and with Na profiling (gradually declining from 150 to 140 mmol/l). Baseline refill rate was 20.1 ± 4.0 ml/min (mean ± SD). Although cool dialysate did not affect refill (22.2 ± 4.1 ml/min, p = 0.27 vs. baseline), Na profiling induced a significant improvement (26.8 ± 3.7 ml/min, p = 0.006 vs. baseline). Using our method to measure absolute plasma refill rate during HD, we demonstrated that Na profiling indeed improves the plasma refill rate. A potential effect of cool dialysate could not be established.

Why Are Sensory Axons More Vulnerable for Ischemia than Motor Axons

Objective In common peripheral neuropathies, sensory symptoms usually prevail over motor symptoms. This predominance of sensory symptoms may result from higher sensitivity of sensory axons to ischemia. Methods We measured median nerve compound sensory action potentials (CSAPs), compound muscle action potentials (CMAPs), and excitability indices in five healthy subjects during forearm ischemia lasting up to disappearance of both CSAPs and CMAPs. Results Ischemia induced: (1) earlier disappearance of CSAPs than CMAPs (mean ± standard deviation 30±5 vs. 46±6 minutes), (2) initial changes compatible with axonal depolarization on excitability testing (decrease in threshold, increase in strength duration time constant (SDTC) and refractory period, and decrease in absolute superexcitability) which were all more prominent in sensory than in motor axons, and (3) a subsequent decrease of SDTC reflecting a decrease in persistent Na+ conductance during continuing depolarisation. Interpretation Our study shows that peripheral sensory axons are more vulnerable for ischemia than motor axons, with faster inexcitability during ischemia. Excitability studies during ischemia showed that this was associated with faster depolarization and faster persistent Na+ channel inactivation in sensory than in motor axons. These findings might be attributed to differences in ion channel composition between sensory and motor axons and may contribute to the predominance of sensory over motor symptoms in common peripheral neuropathies.

Is cold paresis related to axonal depolarization

Cold paresis may occur in multifocal motor neuropathy and lower motor neuron disease. It was proposed to reflect nerve lesions where axons are depolarized due to loss of Na/K‐pump activity. In those circumstances, a further decrease in pump activity by cooling may induce extra depolarization, conduction block, and weakness. Evidence for this hypothesis is incomplete because it is unknown if cold induces depolarization in human motor axons and other factors may contribute to the symptoms. To solve these questions, we examined 10 normal subjects. At 37, 25, 20, and 15°C we assessed: excitability in the median nerve, decrement on 3‐Hz stimulation, pulsed Doppler of a wrist artery, and thenar muscle strength. Cooling induced: (1) findings compatible with axonal depolarization on excitability testing (fanning‐in of threshold electrotonus, steepened current threshold relation, increased refractory period, decreased super‐ and subexcitability), (2) decreased Doppler peak systolic velocity without causing ischemia, (3) decreased muscle strength and impaired muscle relaxation. Decrement tests and compound muscle action potential amplitude remained normal. The excitability findings induced by cooling were best explained by axonal depolarization due to the effect of temperature on Na/K‐pump activity. The induced weakness may be explained not only by this mechanism but also by impaired muscle contraction.

Continuous, online measurement of the absolute plasma refill rate during hemodialysis using feedback regulated ultrafiltration: preliminary results.

Methods to continuously measure absolute refill during dialysis are not available. It would be useful to have such a method because it would allow investigating the mechanism of refill the effect of interventions. We designed a feedback algorithm that adjusts ultrafiltration rate (QUF) according to hemoglobin (Hb) concentration changes in such a way that relative blood volume (BV) remains constant within a narrow target range. In this situation, the generated QUF quantitatively reflects refill. Refill patterns were studied in five hypotension prone patients. In addition, on separate occasions, we studied the effect of antiembolism stockings (AES) and infusion of hydroxy-ethylated starch (HAES) on refill in these patients. Refill during the first hour fell significantly from 21 ± 3 ml/min to 9 ± 2 ml/min (p < 0.05). In the second hour, refill decreased further and became zero in four out of five patients. Neither AES nor HAES measurably affected refill. The marked and rapid fall in refill in the early stages of dialysis suggests untimely depletion of the interstitial compartment and underestimation of dry weight. We propose that continuous, online measurement of refill patterns may be of value for accurate estimation of dry weight in dialysis patients.

Correct positioning of central venous catheters using a new electric method.

Purpose In order to find the correct final position of the tip of a central venous catheter, we have developed a new electric method (the Proximity of Cardiac Motion (PCM) method), designed to work in tandem with the existing ECG-based method. Methods A small, patient-safe, high-frequency current is fed through the catheter (via the saline-filled lumen of the catheter, or a stylet). Simultaneously, the resulting voltage is measured by two electrodes on the frontal thoracic skin. The catheter tip hence functions as a current source inside the vasculature. The cardiac motion produces a variation in the amplitude of the measured voltage in the rhythm of the cardiac cycle, and the strength of this oscillatory variation is proportional to the strength of the incident current field on the heart, which is a rapidly decaying function of the distance between the catheter tip and the cavoatrial junction (CAJ). Hence the strength of this oscillatory variation is a strong indicator for the proximity of the catheter tip with respect to the CAJ. Results The new method has been tested in an animal model, yielding an average final position of the catheter tip of 2.1 cm above the CAJ, with a maximum deviation of 0.5 cm. Conclusions We conclude that the new PCM method can be combined with the existing ECG method, and may potentially have significant added value when the ECG method cannot be applied, for example, in patients with atrial fibrillation or a pacemaker.

Heart rate variability in intensive care unit patients with delirium

Sympathovagal balance, assessed with heart rate variability (HRV), may be altered in intensive care unit (ICU) delirium. HRV was measured in the frequency domain [low frequencies (LF)=0.04-0.15 Hz and high frequencies (HF)=0.15-0.40 Hz] with HF in normalized units (HFnu) to evaluate parasympathetic tone and LF:HF ratio for sympathovagal balance. The authors assessed 726 ICU patients and excluded patients with conditions affecting HRV. No difference could be found between patients with (N=13) and without (N=12) delirium by comparing the mean (±standard deviation) of the HFnu (75±7 versus 68±23) and the LF:HF ratio (-0.7±1.0 versus -0.1±1.1). This study suggests that autonomic function is not altered in ICU delirium.

Comparing excitability at 37°C versus at 20°C: Differences between motor and sensory axons: Motor Versus Sensory Axons

In some peripheral nervous system disorders, cold induces symptoms of muscle weakness without loss of sensation. To understand this selective effect on motor function, it is first essential to delineate the effects of cooling in motor and sensory axons of healthy subjects.

Excitability tests using high-density surface-EMG: A novel approach to studying single motor units

OBJECTIVE To study excitability of single motor units (MUs) using high-density surface-EMG. METHODS Motor unit action potentials (MUAPs) were evoked by submaximal stimulation of the median nerve at the wrist and recorded with a 9 × 14 electrode grid on the skin overlying the thenar muscles. For excitability tests of single MUs, the most optimal specific single-channel surface-EMG signal was selected based on the spatiotemporal profile of single MUs. RESULTS Axonal excitability measures were successfully obtained from 14 single MUs derived from ten healthy subjects. Selecting the optimal single-channel surface-EMG signals minimized interference from other single MUs and improved signal-to-noise ratio. The muscle fiber conduction velocity (MFCV) could also be derived from the unique spatiotemporal profile of single MUs. CONCLUSION High-density surface-EMG helps to isolate single MUAP responses, making it a suitable technique for assessing excitability in multiple single motor axons per nerve. SIGNIFICANCE Our method enables the reliable study of ion-channel dysfunction in single motor axons of nerves without any requirement for specific conditions, such as prominent MU loss or enlarged MUAPs due to collateral sprouting.