Resting-State Network Plasticity Induced by Music Therapy after Traumatic Brain Injury.

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.

Use of black-bone MRI in the diagnosis of the patients with posterior plagiocephaly.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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 body-sized phantom for evaluation of diffusion-weighted MRI data using conventional, readout-segmented, and zoomed echo-planar sequences.

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) mm(2)/s on the average) with readout-segmented EPI as well as ADC variations of approximately 0.1 × 10(-3) mm(2)/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.

Data quality in fMRI and simultaneous EEG-fMRI.

OBJECT: To evaluate functional magnetic resonance imaging (fMRI) and simultaneous electroencephalography (EEG)-fMRI data quality in an organization using several magnetic resonance imaging (MRI) systems. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Safety in simultaneous EEG-fMRI at 3 T: temperature measurements.

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.

Brain magnetic resonance imaging findings six months after critical COVID-19: A prospective cohort study.

BACKGROUND: COVID-19 patients suffered from neurological symptoms in the acute phase. Whether this led to long-term consequences was unknown. We studied long-term brain MRI findings in ICU-treated COVID-19 patients and compared them with findings in groups with less severe acute disease. MATERIALS AND METHODS: In this prospective cohort study, 69 ICU-treated, 46 ward-treated, and 46 home-isolated patients, as well as 53 non-COVID-19 controls, underwent brain MRI six months after acute COVID-19. Plasma neurofilament light chain (NfL), a biomarker of neuroaxonal injury, was measured simultaneously. RESULTS: Ischaemic infarctions existed in 5.8% of ICU-treated patients. Cerebral microbleeds (CMBs) existed in 27 (39.1%) ICU-treated, 13 (28.3%) ward-treated, 8 (17.4%) home-isolated COVID-19 patients, and 12 (22.6%) non-COVID controls. Patients with CMBs were older (p < 0.001), had a higher level of plasma NfL (p = 0.003), and higher supplementary oxygen days (p < 0.001). In multivariable analysis, age (OR 1.06, 95% CI 1.02-1.09) and supplementary oxygen days (OR 1.07, 95% CI 1.02-1.13) were associated with CMBs. The ICU group showed prevalent distribution of CMBs in deep regions. CONCLUSION: Age and supplementary oxygen days were independently associated with CMBs; COVID-19 status showed no association. Accumulation of risk factors in the ICU group may explain the higher prevalence of CMBs. TRIAL REGISTRATION: ClinicalTrials.govNCT04864938, registered February 9, 2021.

Structural Neuroplasticity Effects of Singing in Chronic Aphasia.

Singing-based treatments of aphasia can improve language outcomes, but the neural benefits of group-based singing in aphasia are unknown. Here, we set out to determine the structural neuroplasticity changes underpinning group-based singing-induced treatment effects in chronic aphasia. Twenty-eight patients with at least mild nonfluent poststroke aphasia were randomized into two groups that received a 4-month multicomponent singing intervention (singing group) or standard care (control group). High-resolution T1 images and multishell diffusion-weighted MRI data were collected in two time points (baseline/5 months). Structural gray matter (GM) and white matter (WM) neuroplasticity changes were assessed using language network region of interest-based voxel-based morphometry (VBM) and quantitative anisotropy-based connectometry, and their associations to improved language outcomes (Western Aphasia Battery Naming and Repetition) were evaluated. Connectometry analyses showed that the singing group enhanced structural WM connectivity in the left arcuate fasciculus (AF) and corpus callosum as well as in the frontal aslant tract (FAT), superior longitudinal fasciculus, and corticostriatal tract bilaterally compared with the control group. Moreover, in VBM, the singing group showed GM volume increase in the left inferior frontal cortex (Brodmann area 44) compared with the control group. The neuroplasticity effects in the left BA44, AF, and FAT correlated with improved naming abilities after the intervention. These findings suggest that in the poststroke aphasia group, singing can bring about structural neuroplasticity changes in left frontal language areas and in bilateral language pathways, which underpin treatment-induced improvement in speech production.

Neurological Music Therapy Rebuilds Structural Connectome after Traumatic Brain Injury: Secondary Analysis from a Randomized Controlled Trial.

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.

Neuroanatomical correlates of speech and singing production in chronic post-stroke aphasia.

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.

MRI quality assurance using the ACR phantom in a multi-unit imaging center.

BACKGROUND: Magnetic resonance imaging (MRI) instrumentation is vulnerable to technical and image quality problems, and quality assurance is essential. In the studied regional imaging center the long-term quality assurance has been based on MagNET phantom measurements. American College of Radiology (ACR) has an accreditation program including a standardized image quality measurement protocol and phantom. The ACR protocol includes recommended acceptance criteria for clinical sequences and thus provides possibility to assess the clinical relevance of quality assurance. The purpose of this study was to test the ACR MRI phantom in quality assurance of a multi-unit imaging center. MATERIAL AND METHODS: The imaging center operates 11 MRI systems of three major manufacturers with field strengths of 3.0 T, 1.5 T and 1.0 T. Images of the ACR phantom were acquired using a head coil following the ACR scanning instructions. Both ACR T1- and T2-weighted sequences as well as T1- and T2-weighted brain sequences in clinical use at each site were acquired. Measurements were performed twice. The images were analyzed and the results were compared with the ACR acceptance levels. RESULTS: The acquisition procedure with the ACR phantom was faster than with the MagNET phantoms. On the first and second measurement rounds 91% and 73% of the systems passed the ACR test. Measured slice thickness accuracies were not within the acceptance limits in site T2 sequences. Differences in the high contrast spatial resolution between the ACR and the site sequences were observed. In 3.0 T systems the image intensity uniformity was slightly lower than the ACR acceptance limit. CONCLUSION: The ACR method was feasible in quality assurance of a multi-unit imaging center and the ACR protocol could replace the MagNET phantom tests. An automatic analysis of the images will further improve cost-effectiveness and objectiveness of the ACR protocol.

Comparison of Black Bone MRI and 3D-CT in the preoperative evaluation of patients with craniosynostosis.

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.

Music Therapy Enhances Executive Functions and Prefrontal Structural Neuroplasticity after Traumatic Brain Injury: Evidence from a Randomized Controlled Trial.

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.

Comparison of reconstruction and acquisition choices for quantitative T2* maps and synthetic contrasts.

AIM AND SCOPE: A Gradient Echo Plural Contrast Imaging technique (GEPCI) is a post-processing method, which can be used to obtain quantitative T2* values and generate multiple synthetic contrasts from a single acquisition. However, scan duration and image reconstruction from k-space data present challenges in a clinical workflow. This study aimed at optimizing image reconstruction and acquisition duration to facilitate a post-processing method for synthetic image contrast creation in clinical settings. MATERIALS AND METHODS: This study consists of tests using the American College of Radiology (ACR) image quality phantom, two healthy volunteers, four mild traumatic brain injury patients and four small vessel disease patients. The measurements were carried out on a 3.0 T scanner with multiple echo times. Reconstruction from k-space data and DICOM data with two different coil-channel combination modes were investigated. Partial Fourier techniques were tested to optimize the scanning time. CONCLUSIONS: Sum of squares coil-channel combination produced artifacts in phase images, but images created with adaptive combination were artifact-free. The voxel-wise median signed difference of T2* between the vendor's adaptive channel combination and k-space reconstruction modes was 2.9 ± 0.7 ms for white matter and 4.5 ± 0.6 ms for gray matter. Relative white matter/gray matter contrast of all synthetic images and contrast-to-noise ratio of synthetic T1-weighted images were almost equal between reconstruction modes. Our results indicate that synthetic contrasts can be generated from the vendor's DICOM data with the adaptive combination mode without affecting the quantitative T2* values or white matter/gray matter contrast.

Long-Term Paired Associative Stimulation Enhances Motor Output of the Tetraplegic Hand.

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 < 0.0001, n = 100 muscles from 5 patients). The improvement was significantly higher in PAS-treated than in PNS-treated hands (176 ± 29%, p = 0.046, n = 5 patients). Long-term PAS might be an effective tool for improving motor performance in incomplete chronic SCI patients. Further studies on PAS in larger patient cohorts, with longer stimulation duration and at earlier stages after the injury, are warranted.

Long-term paired associative stimulation can restore voluntary control over paralyzed muscles in incomplete chronic spinal cord injury 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.

Functional plasticity of the motor cortical structures demonstrated by navigated TMS in two patients with epilepsy.

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) in Finland: technological and physical prospects after 20 years of experiences.

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.