Effect of hyoscine butylbromide on prostate multiparametric MRI anatomical and functional image quality.

AIM: To evaluate the effect of the spasmolytic agent hyoscine butylbromide (HBB) on the quality of anatomical and functional imaging of the prostate. MATERIALS AND METHODS: One hundred and seventy-three patients were included in this retrospective study. Eighty-seven patients received intravenous HBB prior to scanning (HBB group) and 86 patients did not (non-HBB group). Multiparametric (mp) 3 T magnetic resonance imaging (MRI) was performed using a 32-channel body coil. Two radiologists independently evaluated the image quality of T2-weighted imaging (WI), diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps, using a five-point Likert scale. DWI was further assessed for distortion and artefact (four-point Likert scale), and T2WI for the presence of motion artefact or blurring. Dynamic contrast-enhanced (DCE) image quality was assessed by recording the number of corrupt contrast curve data points. RESULTS: T2W image quality in the HBB group was significantly higher than in the non-HBB group (3.63±1.11 versus 2.84±0.899); p<0.001. The HBB group also showed significantly less T2W motion and T2W blur than the non-HBB group (23% and 51.7% versus 53.5% and 83.7%, respectively; p<0.001); however, there was no significant improvement in DWI or ADC image quality, or DWI degree of distortion or artefact. There was a trend towards a lower number of corrupted data points from the contrast curve (2.47±2.44 versus 3.68±2.64), but this did not reach significance (p=0.052). CONCLUSION: Administration of HBB significantly improves the image quality of T2WI images. These results provide evidence for the use of HBB in routine patient preparation prior to prostate mpMRI.

Sub-differentiating equivocal PI-RADS-3 lesions in multiparametric magnetic resonance imaging of the prostate to improve cancer detection.

PURPOSE: To evaluate sub-differentiation of PI-RADS-3 prostate lesions using pre-defined T2- and diffusion-weighted (DWI) MRI criteria, to aid the biopsy decision process. METHODS: 143 patients with PIRADS-3 index lesions on MRI underwent targeted transperineal-MR/US fusion biopsy. Radiologists with 2 and 7-years experience performed blinded retrospective second-reads using set criteria and assigned biopsy recommendations. Inter-reader agreement, Gleason score (GS), positive (PPV) predictive values (±95% confidence intervals) were calculated and compared by Fisher's exact test with Bonferroni-Hom correction. RESULTS: 43% (61/143) patients had GS 6-10 and 21% (30/143) GS≥3+4 cancer. For peripheral zone lesions, significant differences in any cancer detection were found for shape (0.26±0.13 geographical vs. 0.69±0.23 rounded; p=0.0055) and ADC (mild 0.21±0.12 vs marked 0.81±0.19; p=0.0001). For transition zone, significantly increased cancer detection was shown for location (anterior 0.63±0.15 vs. mid/posterior 0.31±0.14; p=0.0048), border (pseudo-capsule 0.32±0.14 vs. ill-defined 0.61±0.15; p=0.0092), and ADC (mild 0.35±0.12 vs marked restriction 0.68±0.17; p=0.0057). Biopsy recommendations had 62% inter-reader agreement (89/143). Experienced reader PPVs were significantly higher for any cancer with "biopsy-recommended" 0.61±0.11 vs. "no biopsy" 0.21±0.10 (p=0.0001), and for GS 7-10 cancers: 0.32±0.10 vs. 0.08±0.07, respectively (p=0.0003). CONCLUSION: Identification of certain objective imaging criteria as well as a subjective biopsy recommendation from an experienced radiologist can help to increase the predictive value of equivocal prostate lesions and inform the decision making process of whether or not to biopsy.

Reduction of common synaptic drive to ankle dorsiflexor motoneurons during walking in patients with spinal cord lesion.

It is possible to obtain information about the synaptic drive to motoneurons during walking by analyzing motor-unit coupling in the time and frequency domains. The purpose of the present study was to compare motor-unit coupling during walking in healthy subjects and patients with incomplete spinal cord lesion to obtain evidence of differences in the motoneuronal drive that result from the lesion. Such information is of importance for development of new strategies for gait restoration. Twenty patients with incomplete spinal cord lesion (SCL) participated in the study. Control experiments were performed in 11 healthy subjects. In all healthy subjects, short-term synchronization was evident in the discharge of tibialis anterior (TA) motor units during the swing phase of treadmill walking. This was identified from the presence of a narrow central peak in cumulant densities constructed from paired EMG recordings and from the presence of significant coherence between these signals in the 10- to 20-Hz band. Such indicators of short-term synchrony were either absent or very small in the patient group. The relationship between the amount of short-term synchrony and the magnitude of the 10- to 20-Hz coherence in the patients is discussed in relation to gait ability. It is suggested that supraspinal drive to the spinal cord is responsible for short-term synchrony and coherence in the 10- to 20-Hz frequency band during walking in healthy subjects. Absence or reduction of these features may serve as physiological markers of impaired supraspinal control of gait in SCL patients. Such markers could have diagnostic and prognostic value in relation to the recovery of locomotion in patients with central motor lesions.

Reciprocal inhibition and corticospinal transmission in the arm and leg in patients with autosomal dominant pure spastic paraparesis (ADPSP).

The pathophysiological mechanisms underlying the development of spasticity are not clear, but the excitability of the disynaptic reciprocal inhibitory pathway is affected in many patients with spasticity of different origin. Patients with genetically identified autosomal dominant pure spastic paraparesis (ADPSP) develop spasticity and paresis in the legs, but usually have no symptoms in the arms. Comparison of the spinal and supraspinal control of the legs and arms in these patients may therefore provide valuable information about the pathophysiology of spasticity. In the present study, we tested the hypothesis that one of the pathophysiological mechanisms of spasticity in these patients is abnormal corticospinal transmission and that this may lead to decreased reciprocal inhibition. Ten patients and 15 healthy age-matched control subjects were investigated. The patients were all spastic in the legs (with hyperactive tendon reflexes, increased muscle tone and Babinski sign), but had no neurological symptoms in the arms (except for one patient). Disynaptic reciprocal Ia inhibition of flexor carpi radialis (FCR) and soleus (SOL) motoneurons was measured (as the depression of the background FCR and SOL EMG activity and as the short latency inhibition of the FCR and SOL H-reflex evoked by radial and peroneal nerve stimulation). In addition, the latency of motor evoked potentials (MEPs) in the FCR muscle and the tibialis anterior (TA) muscle was measured. In the patients, the mean reciprocal inhibition was normal in the arms, while it was significantly decreased in the leg compared with the healthy subjects. In the patients, the average latency of MEPs in the FCR muscle was normal, while the latency to the MEP in TA muscle was significantly longer than that found in healthy subjects. Four patients, however, differed from the other patients by having significant reciprocal inhibition in the leg and a significantly shorter latency of TA MEPs than found in the other patients. The six patients without reciprocal inhibition in the leg instead had significant short latency facilitation of the SOL H-reflex and a longer TA MEP latency than seen in the healthy subjects and in the four patients with retained reciprocal inhibition. These findings support the hypothesis that disynaptic reciprocal inhibition and short latency facilitation are involved in the development of spasticity and, furthermore, they suggest a positive correlation between impairment of corticospinal transmission and decrease of reciprocal inhibition/appearance of reciprocal facilitation.

Functional coupling of motor units is modulated during walking in human subjects.

Time- and frequency-domain analysis of the coupling between pairs of electromyograms (EMG) recorded from leg muscles was investigated during walking in healthy human subjects. For two independent surface EMG signals from the tibialis anterior (TA) muscle, coupling estimated from coherence measurements was observed at frequencies

Corticospinal transmission to leg motoneurones in human subjects with deficient glycinergic inhibition.

Normal coordinated movement requires that the activity of antagonistic motoneurones may be depressed at appropriate times during the movement. Both glycinergic and GABAergic inhibitory mechanisms participate in this control. Patients with the major form of hyperekplexia (hereditary startle disease) have impaired inhibition of spinal motoneurones from local glycinergic interneurones and represent an ideal opportunity for studying the role of glycinergic inhibition in the control of antagonistic muscles. In the present study we investigated whether impaired glycinergic inhibition affects the corticospinal control of antagonistic spinal motoneurones in 10 patients with hyperekplexia and whether there are mechanisms that may compensate for the lack of glycinergic inhibition. In healthy subjects transcranial magnetic stimulation (TMS) produced a short-latency inhibition of the soleus H-reflex at rest and during tonic dorsiflexion. This inhibition, which has been shown to be mediated by spinal (glycinergic) inhibitory interneurones, was absent in all four patients in whom this experiment was performed. This confirms that glycinergic transmission is impaired in the patients. During voluntary dorsiflexion subthreshold TMS produced a depression of the ongoing EMG activity in the tibialis anterior (TA) muscle in both healthy subjects and all of the six tested patients. This is consistent with the idea that this EMG depression is caused by activation of cortical (GABAergic) inhibitory interneurones. Cross-correlation analysis revealed normal short-term synchronization of TA motor units accompanied by coherence in the 8-12 Hz and 18-35 Hz frequency bands in the 10 patients. As in healthy subjects, 8-12 Hz coherence accompanied by decreased tendency to discharge synchronously (de-synchronization) was found in recordings from the antagonistic TA and soleus muscles in 2 of the 10 patients. This suggests that glycinergic inhibition is not responsible for de-synchronization of antagonistic motor units, but that other GABAergic-inhibitory mechanisms must be involved. We propose that such mechanisms may compensate for the lack of glycinergic reciprocal inhibition in the hyperekplectic patients and explain why voluntary movements are not more severely affected.

Coupling of antagonistic ankle muscles during co-contraction in humans.

In 35 healthy human subjects coupling of EMGs recorded from the tibialis anterior (TA) and soleus (Sol) muscles during voluntary co-contraction was analysed in the time and frequency domains. Two patterns were observed in different subjects or in the same subject on different occasions. One pattern consisted of central peaks in the cumulant density function of the two signals, which was often accompanied by coherence in the 15-35 Hz frequency band. The other pattern consisted of a central trough in the cumulant density function, which was mostly accompanied by coherence around 10 Hz. When this was the case oscillations were usually observed in the cumulant density function with time lags of 100 ms. Both patterns could be observed in the same subject, but usually not at the same time. Coherence around 10 Hz associated with a central trough in the cumulant density function was less common during weak than during strong co-contraction. The central peak with coherence in the 15-35 Hz frequency band in contrast tended to be most common during weak contraction. There was a tendency for the 10-Hz coherence with central trough to occur when the contractions had been maintained for some time. Both patterns could be observed when sensory feedback in large diameter afferents was blocked by ischaemia. When a central peak with coherence in the 15-35 Hz frequency band was observed for paired TA and Sol EMG recordings (10 out of 19 subjects), a coupling in the same frequency band was also observed between the EMG activities from the two muscles and the EEG activity recorded from the leg area of the motor cortex. When the central trough and the coherence around 10 Hz was observed for the EMG recordings (8 out of 19 subjects), no significant coherence was observed between EEG and EMG in 7 of the 8 subjects. In the last subject coherence around 10 Hz was observed. It is suggested that these findings signify the existence of two different central input systems to antagonistic ankle motoneurones: one input activates one muscle while depressing the antagonist and the other coactivates antagonistic motoneurones. The data suggest that at least the latter input depends on motor cortical activity.

Suppression of EMG activity by transcranial magnetic stimulation in human subjects during walking.

1. The involvement of the motor cortex during human walking was evaluated using transcranial magnetic stimulation (TMS) of the motor cortex at a variety of intensities. Recordings of EMG activity in tibialis anterior (TA) and soleus muscles during walking were rectified and averaged. 2. TMS of low intensity (below threshold for a motor-evoked potential, MEP) produced a suppression of ongoing EMG activity during walking. The average latency for this suppression was 40.0 +/- 1.0 ms. At slightly higher intensities of stimulation there was a facilitation of the EMG activity with an average latency of 29.5 +/- 1.0 ms. As the intensity of the stimulation was increased the facilitation increased in size and eventually a MEP was clear in individual sweeps. 3. In three subjects TMS was replaced by electrical stimulation over the motor cortex. Just below MEP threshold there was a clear facilitation at short latency (approximately 28 ms). As the intensity of the electrical stimulation was reduced the size of the facilitation decreased until it eventually disappeared. We did not observe a suppression of the EMG activity similar to that produced by TMS in any of the subjects. 4. The present study demonstrates that motoneuronal activity during walking can be suppressed by activation of intracortical inhibitory circuits. This illustrates for the first time that activity in the motor cortex is directly involved in the control of the muscles during human walking.

Synchronization of lower limb motor unit activity during walking in human subjects.

Synchronization of motor unit activity was investigated during treadmill walking (speed: 3-4 km/h) in 25 healthy human subjects. Recordings were made by pairs of wire electrodes inserted into the tibialis anterior (TA) muscle and by pairs of surface electrodes placed over this muscle and a number of other lower limb muscles (soleus, gastrocnemius lateralis, gastrocnemius medialis, biceps femoris, vastus lateralis, and vastus medialis). Short-lasting synchronization (average duration: 9.6 +/- 1.1 ms) was observed between spike trains generated from multiunit electromyographic (EMG) signals recorded by the wire electrodes in TA in eight of nine subjects. Synchronization with a slightly longer duration (12.8 +/- 1.2 ms) was also found in 13 of 14 subjects for paired TA surface EMG recordings. The duration and size of this synchronization was within the same range as that observed during tonic dorsiflexion in sitting subjects. There was no relationship between the amount of synchronization and the speed of walking. Synchronization was also observed for pairs of surface EMG recordings from different ankle plantarflexors (soleus, medial gastrocnemius, and lateral gastrocnemius) and knee extensors (vastus lateralis and medialis of quadriceps), but not or rarely for paired recordings from ankle and knee muscles. The data demonstrate that human motor units within a muscle as well as synergistic muscles acting on the same joint receive a common synaptic drive during human gait. It is speculated that the common drive responsible for the motor unit synchronization during gait may be similar to that responsible for short-term synchronization during tonic voluntary contraction.

Expression of intercellular adhesion molecule-1 (ICAM-1) in benign naevi and malignant melanomas.

Intercellular adhesion molecule-1 (ICAM-1) is a membrane-bound glycoprotein that is a ligand for lymphocyte function-associated antigen-1 (LFA-1) and is important for a number of cell adhesions in immune reactions. The molecule is expressed by several cell types (e.g. macrophages, endothelial cells, keratinocytes, melanoma cells and cell lines) and there are some indications that expression of this molecule in melanocytic lesions is confined to malignant tumours and is more pronounced in metastatic and advanced tumours than in earlier lesions. In an attempt to elucidate this issue, we have studied biopsy samples from benign naevi (n = 7) and malignant melanomas (n = 33) regarding reactivity with monoclonal anti-ICAM-1 (CD54). The results indicate that the great majority of malignant melanomas are ICAM-1-positive. The most abundant staining is seen in metastatic melanomas. In primary melanomas, staining is more variable and generally weaker. However, no correlation was found between the degree of ICAM-1 labelling and the degree of tumour invasion. Furthermore, ICAM-1 expression was not confined to malignant lesions, but was also seen in benign naevi. These data contrast with earlier reports and indicate that ICAM-1 expression is unlikely to be of major prognostic or diagnostic value in melanocytic tumours.