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Background: Traumatic brain injury (TBI) is a common and devastating neurological condition, associated often with poor functional outcome and deficits in executive function. Due to the neuropathology of TBI, neuroimaging plays a crucial role in its assessment, and while diffusion MRI has been proposed as a sensitive biomarker, longitudinal studies evaluating treatment-related diffusion MRI changes are scarce. Recent evidence suggests that neurological music therapy can improve executive functions in patients with TBI and that these effects are underpinned by neuroplasticity changes in the brain. However, studies evaluating music therapy induced structural connectome changes in patients with TBI are lacking. Design: Single-blind crossover (AB/BA) randomized controlled trial (NCT01956136). Objective: Here, we report secondary outcomes of the trial and set out to assess the effect of neurological music therapy on structural white matter connectome changes and their association with improved execute function in patients with TBI. Methods: Using an AB/BA design, 25 patients with moderate or severe TBI were randomized to receive a 3-month neurological music therapy intervention either during the first (AB, n = 16) or second (BA, n = 9) half of a 6-month follow-up period. Neuropsychological testing and diffusion MRI scans were performed at baseline and at the 3-month and 6-month stage. Findings: Compared to the control group, the music therapy group increased quantitative anisotropy (QA) in the right dorsal pathways (arcuate fasciculus, superior longitudinal fasciculus) and in the corpus callosum and the right frontal aslant tract, thalamic radiation and corticostriatal tracts. The mean increased QA in this network of results correlated with improved executive function. Conclusions: This study shows that music therapy can induce structural white matter neuroplasticity in the post-TBI brain that underpins improved executive function.

Traumatic brain injury (TBI) is characterized by a complex pattern of abnormalities in resting-state functional connectivity (rsFC) and network dysfunction, which can potentially be ameliorated by rehabilitation. In our previous randomized controlled trial, we found that a 3-month neurological music therapy intervention enhanced executive function (EF) and increased grey matter volume in the right inferior frontal gyrus (IFG) in patients with moderate-to-severe TBI (N=40). Extending this study, we performed longitudinal rsFC analyses of resting-state fMRI data using a ROI-to-ROI approach assessing within-network and between-network rsFC in the frontoparietal (FPN), dorsal attention (DAN), default mode (DMN), and salience (SAL) networks, which all have been associated with cognitive impairment after TBI. We also performed a seed-based connectivity analysis between the right IFG and whole-brain rsFC. The results showed that neurological music therapy increased the coupling between the FPN and DAN as well as between these networks and primary sensory networks. By contrast, the DMN was less connected with sensory networks after the intervention. Similarly, there was a shift towards a less connected state within the FPN and SAL networks, which are typically hyperconnected following TBI. Improvements in EF were correlated with rsFC within the FPN and between the DMN and sensorimotor networks. Finally, in the seed-based connectivity analysis, the right IFG showed increased rsFC with the right inferior parietal and left frontoparietal (Rolandic operculum) regions. Together, these results indicate that the rehabilitative effects of neurological music therapy after TBI are underpinned by a pattern of within- and between-network connectivity changes in cognitive networks as well as increased connectivity between frontal and parietal regions associated with music processing.

Summary Purpose Black Bone (BB) magnetic resonance imaging (MRI) is a nonionizing imaging method and a recent alternative to computed tomography (CT) in the examination of cranial deformities. The purpose of this study was to compare BB-MRI and routine 3D-CT in the preoperative evaluation of patients with craniosynostosis. Methods At our center, we have routinely performed preoperative CT of the skull and brain MRI for patients with clinical suspicion of craniosynostosis. We recently changed our MRI protocol into one that includes sequences for the evaluation of both brain anatomy and skull bone and sutures by BB-MRI. A semi-automatic skull segmentation algorithm was developed to facilitate visualization. Both BB-MRI and 3D-CT were performed on 9 patients with clinical craniosynostosis, and the images were evaluated by two craniofacial surgeons, one pediatric neurosurgeon, and two neuroradiologists. Results We obtained informative 3D images using BB-MRI. Six (6/9) patients had scaphocephaly, 1 (1/9) patient had unicoronal synostosis, and 2 (2/9) patients had lambdoid synostosis. The affected synostotic sutures could be identified both by BB-MRI and by 3D-CT in all patients. Intra-rater and inter-rater reliability for rating the calvarial sutures was high. However, the reliability for rating the intracranial impressions was low by both imaging methods. Conclusion BB-MRI is an alternative to 3D-CT in the preoperative evaluation of patients with craniosynostosis. BB-MRI provides information not only on cranial sutures and intracranial impressions but also on the brain structure in one imaging session. This method can replace ionizing radiation-based methods in analyzing skull deformities.

Traumatic brain injury (TBI) causes lifelong cognitive deficits, particularly impairments of executive functioning (EF). Musical training and music-based rehabilitation have been shown to enhance cognitive functioning and neuroplasticity, but the potential rehabilitative effects of music in TBI are still largely unknown. The aim of the present crossover randomized controlled trial (RCT) was to determine the clinical efficacy of music therapy on cognitive functioning in TBI and to explore its neural basis. Using an AB/BA design, 40 patients with moderate or severe TBI were randomized to receive a 3-month neurological music therapy intervention either during the first (AB, n = 20) or second (BA, n = 20) half of a 6-month follow-up period. Neuropsychological and motor testing and magnetic resonance imaging (MRI) were performed at baseline and at the 3-month and 6-month stage. Thirty-nine subjects who participated in baseline measurement were included in an intention-to-treat analysis using multiple imputation. Results showed that general EF (as indicated by the Frontal Assessment Battery [FAB]) and set shifting improved more in the AB group than in the BA group over the first 3-month period and the effect on general EF was maintained in the 6-month follow-up. Voxel-based morphometry (VBM) analysis of the structural MRI data indicated that gray matter volume (GMV) in the right inferior frontal gyrus (IFG) increased significantly in both groups during the intervention versus control period, which also correlated with cognitive improvement in set shifting. These findings suggest that neurological music therapy enhances EF and induces fine-grained neuroanatomical changes in prefrontal areas

Ionising radiation exposure is especially harmful to brain development. The purpose of this study was to evaluate whether black-bone (BB) magnetic resonance imaging (MRI), a non-ionising imaging method, offers an alternative to ionising imaging methods such as computed tomography (CT) in the examination of cranial deformities. From 2012 to 2014, a total of 408 children were referred to the Craniofacial Centre at the Helsinki University Hospital for further examination due to flatness of the posterior skull. Fifteen of these patients required further diagnostic imaging. To avoid ionising radiation, we used an MRI protocol that included sequences for evaluation of both brain anatomy and skull bone and sutures by BB-MRI. A semi-automatic skull segmentation algorithm was developed to facilitate the visualisation. Two patients with scaphocephaly were included in the study to confirm the ability to differentiate synostosis with BB-MRI. We obtained informative 3D images using BB-MRI. Seven patients (7/15, 46.7%) had plagiocephaly on the right side and seven on the left side (7/15, 46.7%). One patient (1/15, 6.7%) had symmetric posterior flatness affecting both sides. Neither structural nor signal-intensity alterations of the brain were detected in visual analysis. BB-MRI provides an alternative to CT when imaging craniofacial deformities. BB-MRI provides not only high-quality 3D-reconstructed imaging of the bony structures and sutures but also information on brain structure in one imaging session. With further development, this method could replace ionising radiation-based methods in analysing deformities of the skull.

A large proportion of spinal cord injuries (SCI) are incomplete. Even in clinically complete injuries, silent non-functional connections can be present. Therapeutic approaches that can strengthen transmission in weak neural connections to improve motor performance are needed. Our aim was to determine whether long-term delivery of paired associative stimulation (PAS, a combination of transcranial magnetic stimulation [TMS] with peripheral nerve stimulation [PNS]) can enhance motor output in the hands of patients with chronic traumatic tetraplegia, and to compare this technique with long-term PNS. Five patients (4 males; age 38-68, mean 48) with no contraindications to TMS received 4 weeks (16 sessions) of stimulation. PAS was given to one hand and PNS combined with sham TMS to the other hand. Patients were blinded to the treatment. Hands were selected randomly. The patients were evaluated by a physiotherapist blinded to the treatment. The follow-up period was 1 month. Patients were evaluated with Daniels and Worthingham's Muscle Testing (0-5 scale) before the first stimulation session, after the last stimulation session, and 1 month after the last stimulation session. One month after the last stimulation session, the improvement in the PAS-treated hand was 1.02 +/- 0.17 points (p

Background Recently, navigated transcranial magnetic stimulation (nTMS) has been suggested to be useful in preoperative functional localization of motor cortex in patients having tumors close to the somatomotor cortex. Resection of tumors in anatomically predicted eloquent areas without adverse effects have emphasized functional plasticity elicited by intracranial pathology. Objective To describe functional plasticity of motor cortex indicated by nTMS in two patients with epilepsy. Methods nTMS, functional MRI (fMRI), diffusion-tensor (DT)-tractography and magnetoencephalography (MEG) were utilized to preoperatively localize motor cortical areas in the workup for epilepsy surgery. The localizations were compared with each other, with the cortical anatomical landmarks, and in one patient with invasive electrical cortical stimulation (ECS). Results In two out of 19 studied patients, nTMS identified motor cortical sites that differed from those indicated by anatomical landmarks. In one patient, nTMS activated preferentially premotor cortex rather than pathways originating from the precentral gyrus. MEG and fMRI localizations conformed with nTMS whereas ECS localized finger motor function into the precentral gyrus. Resection of the area producing motor responses in biphasic nTMS did not produce a motor deficit. In the other patient, nTMS indicated abnormal ipsilateral hand motor cortex localization and confirmed the functionality of aberrant motor cortical representations of the left foot also indicated by fMRI and DT-tractography. Conclusion nTMS may reveal the functional plasticity and shifts of motor cortical function. Epileptic foci may modify cortical inhibition and the nTMS results. Therefore, in some patients with epilepsy, the nTMS results need to be interpreted with caution with regard to surgical planning.

Boron Neutron Capture Therapy (BNCT) is a binary radiotherapy method developed to treat patients with certain malignant tumours. To date, over 300 treatments have been carried out at the Finnish BNCT facility in various on-going and past clinical trials. In this technical review, we discuss our research work in the field of medical physics to form the groundwork for the Finnish BNCT patient treatments, as well as the possibilities to further develop and optimize the method in the future. Accordingly, the following aspects are described: neutron sources, beam dosimetry, treatment planning, boron imaging and determination, and finally the possibilities to detect the efficacy and effects of BNCT on patients.

Emerging therapeutic strategies for spinal cord injury aim at sparing or restoring at least part of the corticospinal tract at the acute stage. Hence, approaches that strengthen the weak connections that are spared or restored are crucial. Transient plastic changes in the human corticospinal tract can be induced through paired associative stimulation, a noninvasive technique in which transcranial magnetic brain stimulation is synchronized with electrical peripheral nerve stimulation. A single paired associative stimulation session can induce transient plasticity in spinal cord injury patients. It is not known whether paired associative stimulation can strengthen neuronal connections persistently and have therapeutic effects that are clinically relevant. We recruited two patients with motor-incomplete chronic (one para- and one tetraplegic) spinal cord injuries. The patients received paired associative stimulation for 20-24 weeks. The paraplegic patient, previously paralyzed below the knee level, regained plantarflexion and dorsiflexion of the ankles of both legs. The tetraplegic patient regained grasping ability. The newly acquired voluntary movements could be performed by the patients in the absence of stimulation and for at least 1 month after the last stimulation session. In this unblinded proof-of-principle demonstration in two subjects, long-term paired associative stimulation induced persistent and clinically relevant strengthening of neural connections and restored voluntary movement in previously paralyzed muscles. Further study is needed to confirm whether long-term paired associative stimulation can be used in rehabilitation after spinal cord injury by itself and, possibly, in combination with other therapeutic strategies.

Diffusion Tensor Imaging (DTI) is commonly challenged by subject motion during data acquisition, which often leads to corrupted image data. Currently used procedure in DTI analysis is to correct or completely reject such data before tensor estimations, however assessing the reliability and accuracy of the estimated tensor in such situations has evaded previous studies. This work aims to define the loss of data accuracy with increasing image rejections, and to define a robust method for assessing reliability of the result at voxel level. We carried out simulations of every possible sub-scheme (N=1,073,567,387) of Jones30 gradient scheme, followed by confirming the idea with MRI data from four newborn and three adult subjects. We assessed the relative error of the most commonly used tensor estimates for DTI and tractography studies, fractional anisotropy (FA) and the major orientation vector (V1), respectively. The error was estimated using two measures, the widely used electric potential (EP) criteria as well as the rotationally variant condition number (CN). Our results show that CN and EP are comparable in situations with very few rejections, but CN becomes clearly more sensitive to depicting errors when more gradient vectors and images were rejected. The error in FA and V1 was also found depend on the actual FA level in the given voxel; low actual FA levels were related to high relative errors in the FA and V1 estimates. Finally, the results were confirmed with clinical MRI data. This showed that the errors after rejections are, indeed, inhomogeneous across brain regions. The FA and V1 errors become progressively larger when moving from the thick white matter bundles towards more superficial subcortical structures. Our findings suggest that i) CN is a useful estimator of data reliability at voxel level, and ii) DTI preprocessing with data rejections leads to major challenges when assessing brain tissue with lower FA levels, such as all newborn brain, as well as the adult superficial, subcortical areas commonly traced in precise connectivity analyses between cortical regions.

Background Abdominal diffusion-weighted imaging (DWI) has been rapidly increasing during the last few years. For the evaluation of new DWI techniques, the development of suitable phantoms and quality assurance methods is important. Purpose To construct a body-diameter phantom for abdominal DWI and study the impact of different acquisition options on image quality. Material and Methods A phantom with a diameter of 31 cm and a volume of 26 L was constructed, containing four samples representing a clinically relevant range of apparent diffusion coefficient (ADC) values. Measurements were carried out on 1.5T and 3.0T MRI systems using conventional echo-planar imaging (EPI), readout-segmented EPI, and zoomed EPI (3.0T) sequences. The effects of parallel imaging, coil intensity normalization, and patient-specific B1 shim (3.0T) were also examined. ADC values and signal-to-noise ratios of the samples were measured, and the level of artifacts was visually evaluated. Results The agreement of ADC values between different acquisition options was generally good, but higher values (by 0.07 × 10–3 mm2/s on the average) with readout-segmented EPI as well as ADC variations of approximately 0.1 × 10–3 mm2/s in slice direction were observed. The image artifacts were reduced by using patient-specific B1 shim, readout-segmented EPI, or zoomed EPI. Conclusion The body-sized phantom demonstrated well the expected image artifacts in DWI with large field of view. The use of patient-specific B1 shim, readout-segmented EPI, or zoomed EPI improved image quality of DWI in this study.

Objectives Simultaneous EEG–fMRI is increasingly used in presurgical evaluation of epilepsy patients. The MR environment causes massive gradient artefacts and cardioballistic artefacts (BCG) to the recorded EEG signal, which must be corrected for, to make the reading of the EEG possible. This study aims to see, whether residual artefacts could disturb the specialist interpreting the EEG, even after apparently successful correction of the artefacts via widely accepted methods. Methods We studied 20 epilepsy patients who had undergone a simultaneous EEG–fMRI exam. The EEG was corrected for gradient artefact by the average artefact subtraction method, and the BCG was corrected with ICA. The EEG was read by a specialist, who marked all interictal epileptiform events to the EEG recording. Using simple statistical analysis methods, namely standard binomial distribution for the gradient artefact and Pearson’s chi-squared test for the BCG, we tested for the correlation of the epileptiform events to the artefactual sources. Results Nine of the 20 exams had a sufficient number of epileptiform events for analysis. Correlation to the gradient artefact was found in two patient cases ( p ⩽ 0.05 ), and correlation to the BCG was found in two cases ( p 0.001 ), with one patient’s data correlating to both artefact sources. Discussion The results indicate that initially acceptable EEG-fMRI data can contain residual artefacts that are visually hard to detect. Conclusions/significance We propose that all simultaneous EEG–fMRI exams should be controlled for possible hidden correlations to known artefactual sources, to ensure best possible patient outcomes especially in relation to brain surgery.

Background In simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), safety of the EEG equipment is ensured by the manufacturer only for localizers and fMRI sequences. To conduct a clinically feasible simultaneous EEG-fMRI study, other sequences, e.g. anatomical and B0-correction sequences, have to be acquired in the same imaging session. Purpose To measure the temperature increase of the electrodes in different size EEG caps in a phantom and volunteers during magnetic resonance imaging (MRI) sequences typically used in clinical studies. Material and Methods A phantom with EEG caps of size 52, 56, and 60 was imaged using several sequences in two 3 T MRI scanners to determine the maximum and average temperature increases in the electrodes. Additionally, three volunteer studies were performed for the EEG caps of sizes 56 and 60. The sequences were gradient echo based echo planar imaging sequence, T2-weighted turbo spin echo (T2-TSE), spin echo multiecho for B0-correction, diffusion tensor imaging and T1-weighted 3D sequences. Results In phantom studies the maximum temperature increase was 4.1℃ with a mean of 1.2 ± 1.1℃. In volunteer studies, the maximum temperature measured was 35.6℃ and the maximum temperature rise was 2.1℃ with a mean of 0.9 ± 0.7℃. Both were observed with a T2-TSE sequence. Conclusion The temperature of the electrodes did not exceed the limits set by the IEC 60601-1 standard (43℃) or manufacturer (45℃), thus indicating a safe EEG-fMRI protocol in this respect.

To evaluate functional magnetic resonance imaging (fMRI) and simultaneous electroencephalography (EEG)–fMRI data quality in an organization using several magnetic resonance imaging (MRI) systems. Functional magnetic resonance imaging measurements were carried out twice with a uniform gel phantom on five different MRI systems with field strengths of 1.5 and 3.0 T. Several image quality parameters were measured with automatic analysis software. For simultaneous EEG–fMRI, data quality was evaluated on 3.0 T systems, and the phantom results were compared to data on human volunteers. The fMRI quality parameters measured with different MRI systems were on an acceptable level. The presence of the EEG equipment caused superficial artifacts on the phantom image. The typical artifact depth was 15 mm, and no artifacts were observed in the brain area in the images of volunteers. Average signal-to-noise ratio (SNR) reduction in the phantom measurements was 15 %, a reduction of SNR similar to that observed in the human data. We also detected minor changes in the noise of the EEG signal during the phantom measurement. The phantom proved valuable in the successful evaluation of the data quality of fMRI and EEG–fMRI. The results fell within acceptable limits. This study demonstrated a repeatable method to measure and follow up on the data quality of simultaneous EEG–fMRI.

A classical observation in neurology is that aphasic stroke patients with impairments in speech production can nonetheless sing the same utterances. This preserved ability suggests a distinctive neural architecture for singing that could contribute to speech recovery. However, to date, these structural correlates remain unknown. Here, we combined a multivariate lesion–symptom mapping and voxel-based morphometry approach to analyse the relationship between lesion patterns and grey matter volume and production rate in speech and singing tasks. Lesion patterns for spontaneous speech and cued repetition extended into frontal, temporal and parietal areas typically reported within the speech production network. Impairment in spontaneous singing was associated with damage to the left anterior–posterior superior and middle temporal gyri. Preservation of grey matter volume in the same regions where damage led to poor speech and singing production supported better performance in these tasks. When dividing the patients into fluent and dysfluent singers based on the singing performance from demographically matched controls, we found that the preservation of the left middle temporal gyrus was related to better spontaneous singing. These findings provide insights into the structural correlates of singing in chronic aphasia and may serve as biomarkers to predict treatment response in clinical trials using singing-based interventions for speech rehabilitation.