Fatigue following head and neck cancer radiotherapy: a systematic review of dose correlates.

INTRODUCTIONS: Radical radiotherapy (RT) is the cornerstone of Head and Neck (H&N) cancer treatment, but it often leads to fatigue due to irradiation of brain structures, impacting patient quality of life. OBJECTIVE: This study aimed to systematically investigate the dose correlates of fatigue after H&N RT in brain structures. METHODS: The systematic review included studies that examined the correlation between fatigue outcomes in H&N cancer patients undergoing RT at different time intervals and brain structures. PubMed, Scopus, and WOS databases were used in the systematic review. A methodological quality assessment of the included studies was conducted following the PRISMA guidelines. After RT, the cohort of H&N cancer patients was analyzed for dose correlations with brain structures and substructures, such as the posterior fossa, brainstem, cerebellum, pituitary gland, medulla, and basal ganglia. RESULT: Thirteen studies meeting the inclusion criteria were identified in the search. These studies evaluated the correlation between fatigue and RT dose following H&N RT. The RT dose ranged from 40 Gy to 70 Gy. Most of the studies indicated a correlation between the trajectory of fatigue and the dose effect, with higher levels of fatigue associated with increasing doses. Furthermore, five studies found that acute and late fatigue was associated with dose volume in specific brain structures, such as the brain stem, posterior fossa, cerebellum, pituitary gland, hippocampus, and basal ganglia. CONCLUSION: Fatigue in H&N RT patients is related to the radiation dose received in specific brain areas, particularly in the posterior fossa, brain stem, cerebellum, pituitary gland, medulla, and basal ganglia. Dose reduction in these areas may help alleviate fatigue. Monitoring fatigue in high-risk patients after radiation therapy could be beneficial, especially for those experiencing late fatigue.

Quality of Life for Head and Neck Cancer Patients: A 10-Year Bibliographic Analysis.

Head and neck cancers (HNCs) have a profound impact on patients, affecting not only their physical appearance but also fundamental aspects of their daily lives. This bibliometric study examines the landscape of scientific research pertaining to the quality of life (QoL) among head and neck cancer (HNC) patients. By employing data and bibliometric analysis derived from the Web of Science Core Collection (WOS-CC) and employing R-package and VOSviewer for visualization, the study assesses the current status of and prominent areas of focus within the literature over the past decade. The analysis reveals noteworthy countries, journals, and institutions that have exhibited notable productivity in this research domain between 2013 and 2022. Notably, the United States, the Supportive Care in Cancer journal, and the University of Pittsburgh emerged as the leading contributors. Moreover, there was a discernible shift, with an increasing focus on the significance of QoL within the survivorship context, exemplified by the emergence and subsequent peak of related keywords in 2020 and the subsequent year, respectively. The temporal analysis additionally reveals a transition towards specific QoL indices, such as dysphagia and oral mucositis. Therefore, the increasing relevance of survivorship further underscores the need for studies that address the associated concerns and challenges faced by patients.

The Applications of High-Intensity Focused Ultrasound (HIFU) Ablative Therapy in the Treatment of Primary Breast Cancer: A Systematic Review.

BACKGROUND: This study evaluates the role of high-intensity focused ultrasound (HIFU) ablative therapy in treating primary breast cancer. METHODS: PubMed and Scopus databases were searched according to the PRISMA guidelines to identify studies from 2002 to November 2022. Eligible studies were selected based on criteria such as experimental study type, the use of HIFU therapy as a treatment for localised breast cancer with objective clinical evaluation, i.e., clinical, radiological, and pathological outcomes. Nine studies were included in this study. RESULTS: Two randomised controlled trials and seven non-randomised clinical trials fulfilled the inclusion criteria. The percentage of patients who achieved complete (100%) coagulation necrosis varied from 17% to 100% across all studies. Eight of the nine studies followed the treat-and-resect protocol in which HIFU-ablated tumours were surgically resected for pathological evaluation. Most breast cancers were single, solitary, and palpable breast tumours. Haematoxylin and eosin stains used for histopathological evaluation showed evidence of coagulation necrosis. Radiological evaluation by MRI showed an absence of contrast enhancement in the HIFU-treated tumour and 1.5 to 2 cm of normal breast tissue, with a thin peripheral rim of enhancement indicative of coagulation necrosis. All studies did not report severe complications, i.e., haemorrhage and infection. Common complications related to HIFU ablation were local mammary oedema, pain, tenderness, and mild to moderate burns. Only one third-degree burn was reported. Generally, the cosmetic outcome was good. The five-year disease-free survival rate was 95%, as reported in two RCTs. CONCLUSIONS: HIFU ablation can induce tumour coagulation necrosis in localised breast cancer, with a favourable safety profile and cosmetic outcome. However, there is variable evidence of complete coagulation necrosis in the HIFU-treated tumour. Histopathological evidence of coagulation necrosis has been inconsistent, and there is no reliable radiological modality to assess coagulation necrosis confidently. Further exploration is needed to establish the accurate ablation margin with a reliable radiological modality for treatment and follow-up. HIFU therapy is currently limited to single, palpable breast tumours. More extensive and randomised clinical trials are needed to evaluate HIFU therapy for breast cancer, especially where the tumour is left in situ.

The Assessment of White Matter Integrity Alteration Pattern in Patients with Brain Tumor Utilizing Diffusion Tensor Imaging: A Systematic Review.

Alteration in the surrounding brain tissue may occur in the presence of a brain tumor. The present study aims to assess the characteristics and criteria of the pattern of white matter tract microstructure integrity alteration in brain tumor patients. The Scopus, PubMed/Medline, and Web of Science electronic databases were searched for related articles based on the guidelines established by PRISMA. Twenty-five studies were selected on the morphological changes of white matter tract integrity based on the differential classification of white matter tract (WMT) patterns in brain tumor patients through diffusion tensor imaging (DTI). The characterization was based on two criteria: the visualization of the tract-its orientation and position-and the DTI parameters, which were the fractional anisotropy and apparent diffusion coefficient. Individual evaluations revealed no absolute, mutually exclusive type of tumor in relation to morphological WMT microstructure integrity changes. In most cases, different types and grades of tumors have shown displacement or infiltration. Characterizing morphological changes in the integrity of the white matter tract microstructures is vital in the diagnostic and prognostic evaluation of the tumor's progression and could be a potential assessment for the early detection of possible neurological defects that may affect the patient, as well as aiding in surgery decision-making.

Role of resting-state functional MRI in detecting brain functional changes following radiotherapy for head and neck cancer: a systematic review and meta-analysis.

PURPOSE: Increasing evidence implicates changes in brain function following radiotherapy for head and neck cancer as precursors for brain dysfunction. These changes may thus be used as biomarkers for early detection. This review aimed to determine the role of resting-state functional magnetic resonance imaging (rs-fMRI) in detecting brain functional changes. METHODS: A systematic search was performed in the PubMed, Scopus, and Web of Science (WoS) databases in June 2022. Patients with head and neck cancer treated with radiotherapy and periodic rs-fMRI assessments were included. A meta-analysis was performed to determine the potential of rs-fMRI for detecting brain changes. RESULTS: Ten studies with a total of 513 subjects (head and neck cancer patients, n = 437; healthy controls, n = 76) were included. A significance of rs-fMRI for detecting brain changes in the temporal and frontal lobes, cingulate cortex, and cuneus was demonstrated in most studies. These changes were reported to be associated with dose (6/10 studies) and latency (4/10 studies). A strong effect size (r = 0.71, p < 0.001) between rs-fMRI and brain changes was also reported, suggesting rs-fMRI's capability for monitoring brain alterations. CONCLUSION: Resting-state functional MRI is a promising tool for detecting brain functional changes following head and neck radiotherapy. These changes are correlated with latency and prescription dose.

Delta-radiomics-based models for toxicity prediction in radiotherapy: A systematic review and meta-analysis.

INTRODUCTION: Delta-radiomics models are potentially able to improve the treatment assessment than single-time point features. The purpose of this study is to systematically synthesize the performance of delta-radiomics-based models for radiotherapy (RT)-induced toxicity. METHODS: A literature search was performed following the PRISMA guidelines. Systematic searches were performed in PubMed, Scopus, Cochrane and Embase databases in October 2022. Retrospective and prospective studies on the delta-radiomics model for RT-induced toxicity were included based on predefined PICOS criteria. A random-effect meta-analysis of AUC was performed on the performance of delta-radiomics models, and a comparison with non-delta radiomics models was included. RESULTS: Of the 563 articles retrieved, 13 selected studies of RT-treated patients on different types of cancer (HNC = 571, NPC = 186, NSCLC = 165, oesophagus = 106, prostate = 33, OPC = 21) were eligible for inclusion in the systematic review. Included studies show that morphological and dosimetric features may improve the predictive model performance for the selected toxicity. Four studies that reported both delta and non-delta radiomics features with AUC were included in the meta-analysis. The AUC random effects estimate for delta and non-delta radiomics models were 0.80 and 0.78 with heterogeneity, I2 of 73% and 27% respectively. CONCLUSION: Delta-radiomics-based models were found to be promising predictors of predefined end points. Future studies should consider using standardized methods and radiomics features and external validation to the reviewed delta-radiomics model.

Quality of Life and Patient-Reported Outcomes Following Proton Therapy for Oropharyngeal Carcinoma: A Systematic Review.

BACKGROUND: Complex anatomy surrounding the oropharynx makes proton therapy (PT), especially intensity-modulated PT (IMPT), a potentially attractive option due to its ability to reduce the volume of irradiated healthy tissues. Dosimetric improvement may not translate to clinically relevant benefits. As outcome data are emerging, we aimed to evaluate the evidence of the quality of life (QOL) and patient-reported outcomes (PROs) following PT for oropharyngeal carcinoma (OC). MATERIALS AND METHODS: We searched PubMed and Scopus electronic databases (date: 15 February 2023) to identify original studies on QOL and PROs following PT for OC. We employed a fluid strategy in the search strategy by tracking citations of the initially selected studies. Reports were extracted for information on demographics, main results, and clinical and dose factor correlates. Quality assessment was performed using the NIH's Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The PRISMA guidelines were followed in the preparation of this report. RESULTS: Seven reports were selected, including one from a recently published paper captured from citation tracking. Five compared PT and photon-based therapy, although none were randomized controlled trials. Most endpoints with significant differences favored PT, including xerostomia, cough, need for nutritional supplements, dysgeusia, food taste, appetite, and general symptoms. However, some endpoints favored photon-based therapy (sexual symptoms) or showed no significant difference (e.g., fatigue, pain, sleep, mouth sores). The PROs and QOL improve following PT but do not appear to return to baseline. CONCLUSION: Evidence suggests that PT causes less QOL and PRO deterioration than photon-based therapy. Biases due to the non-randomized study design remain obstacles to a firm conclusion. Whether or not PT is cost-effective should be the subject of further investigation.

Functional Alteration in the Brain Due to Tumour Invasion in Paediatric Patients: A Systematic Review.

Working memory, language and speech abilities, motor skills, and visual abilities are often impaired in children with brain tumours. This is because tumours can invade the brain's functional areas and cause alterations to the neuronal networks. However, it is unclear what the mechanism of tumour invasion is and how various treatments can cause cognitive impairment. Therefore, this study aims to systematically evaluate the effects of tumour invasion on the cognitive, language, motor, and visual abilities of paediatric patients, as well as discuss the alterations and modifications in neuronal networks and anatomy. The electronic database, PubMed, was used to find relevant studies. The studies were systematically reviewed based on the type and location of brain tumours, cognitive assessment, and pre- and post-operative deficits experienced by patients. Sixteen studies were selected based on the inclusion and exclusion criteria following the guidelines from PRISMA. Most studies agree that tumour invasion in the brain causes cognitive dysfunction and alteration in patients. The effects of a tumour on cognition, language, motor, and visual abilities depend on the type of tumour and its location in the brain. The alteration to the neuronal networks is also dependent on the type and location of the tumour. However, the default mode network (DMN) is the most affected network, regardless of the tumour type and location.Furthermore, our findings suggest that different treatment types can also contribute to patients' cognitive function to improve or deteriorate. Deficits that persisted or were acquired after surgery could result from surgical manipulation or the progression of the tumour's growth. Meanwhile, recovery from the deficits indicated that the brain has the ability to recover and reorganise itself.

Remote assessment of cognition and quality of life following radiotherapy for glioma: deep-learning-based predictive models and MRI correlates.

BACKGROUND: Glioma irradiation often unavoidably damages the brain volume and affects cognition. This study aims to evaluate the relationship of remote cognitive assessments in determining cognitive impairment of irradiated glioma patients in relation to the quality of life and MRI changes. METHODS: Thirty patients (16-76 aged) with two imaging (pre- and post-RT) and completed cognitive assessments were recruited. Cerebellum, right and left temporal lobes, corpus callosum, amygdala and spinal cord were delineated and their dosimetry parameters were collected. Cognitive assessments were given post-RT via telephone (Telephone Interview Cognitive Status (TICS), Telephone Montreal Cognitive Assessment (T-MoCA), Telephone Mini Addenbrooke's Cognitive Examination (Tele-MACE)). Regression models and deep neural network (DNN) were used to evaluate the relationship between brain volume, cognition and treatment dose in patients. RESULTS: Cognitive assessments were highly inter-correlated (r > 0.9) and impairment was shown between pre- and post-RT findings. Brain volume atrophy was shown post-RT, and cognitive impairments were correlated with radiotherapy-associated volume atrophy and dose-dependent in the left temporal lobe, corpus callosum, cerebellum and amygdala. DNN showed a good area under the curve for cognitive prediction; TICS (0.952), T-MoCA (0.909) and Tele-MACE (0.822). CONCLUSIONS: Cognition can be evaluated remotely in which radiotherapy-related brain injury is dose-dependent and volume-dependent. Prediction models can assist in the early identification of patients at risk for neurocognitive decline following RT for glioma, thus facilitating potential treatment interventions.

Remote assessment of cognition and quality of life following radiotherapy for nasopharyngeal carcinoma: deep-learning-based predictive models and MRI correlates.

PURPOSE: Irradiation of the brain regions from nasopharyngeal carcinoma (NPC) radiotherapy (RT) is frequently unavoidable, which may result in radiation-induced cognitive deficit. Using deep learning (DL), the study aims to develop prediction models in predicting compromised cognition in patients following NPC RT using remote assessments and determine their relation to the quality of life (QoL) and MRI changes. METHODS: Seventy patients (20-76 aged) with MRI imaging (pre- and post-RT (6 months-1 year)) and complete cognitive assessments were recruited. Hippocampus, temporal lobes (TLs), and cerebellum were delineated and dosimetry parameters were extracted. Assessments were given post-RT via telephone (Telephone Interview Cognitive Status (TICS), Telephone Montreal Cognitive Assessment (T-MoCA), Telephone Mini Addenbrooke's Cognitive Examination (Tele-MACE), and QLQ-H&N 43). Regression and deep neural network (DNN) models were used to predict post-RT cognition using anatomical and treatment dose features. RESULTS: Remote cognitive assessments were inter-correlated (r > 0.9). TLs showed significance in pre- and post-RT volume differences and cognitive deficits, that are correlated with RT-associated volume atrophy and dose distribution. Good classification accuracy based on DNN area under receiver operating curve (AUROC) for cognitive prediction (T-MoCA AUROC = 0.878, TICS AUROC = 0.89, Tele-MACE AUROC = 0.919). CONCLUSION: DL-based prediction models assessed using remote assessments can assist in predicting cognitive deficit following NPC RT. Comparable results of remote assessments in assessing cognition suggest its possibility in replacing standard assessments. IMPLICATIONS FOR CANCER SURVIVORS: Application of prediction models in individual patient enables tailored interventions to be provided in managing cognitive changes following NPC RT.

Ultrasonographic Evaluation of Skin Toxicity Following Radiotherapy of Breast Cancer: A Systematic Review.

The present review aimed to systematically review skin toxicity changes following breast cancer radiotherapy (RT) using ultrasound (US). PubMed and Scopus databases were searched according to PRISMA guidelines. The characteristics of the selected studies, measured parameters, US skin findings, and their association with clinical assessments were extracted. Seventeen studies were included with a median sample size of 29 (range 11-166). There were significant US skin changes in the irradiated skin compared to the nonirradiated skin or baseline measurements. The most observed change is skin thickening secondary to radiation-induced oedema, except one study found skin thinning after pure postmastectomy RT. However, eight studies reported skin thickening predated RT attributed to axillary surgery. Four studies used US radiofrequency (RF) signals and found a decrease in the hypodermis's Pearson correlation coefficient (PCC). Three studies reported decreased dermal echogenicity and poor visibility of the dermis-subcutaneous fat boundary (statistically analysed by one report). The present review revealed significant ultrasonographic skin toxicity changes in the irradiated skin most commonly skin thickening. However, further studies with large cohorts, appropriate US protocol, and baseline evaluation are needed. Measuring other US skin parameters and statistically evaluating the degree of the association with clinical assessments are also encouraged.

The Utilization of Diffusion Tensor Imaging as an Image-Guided Tool in Brain Tumor Resection Surgery: A Systematic Review.

The diffusion tensor imaging technique has been recognized as a neuroimaging tool for in vivo visualization of white matter tracts. However, DTI is not a routine procedure for preoperative planning for brain tumor resection. Our study aimed to systematically evaluate the effectiveness of DTI and the outcomes of surgery. The electronic databases, PubMed/MEDLINE and Scopus, were searched for relevant studies. Studies were systematically reviewed based on the application of DTI in pre-surgical planning, modification of operative planning, re-evaluation of preoperative DTI data intraoperatively, and the outcome of surgery decisions. Seventeen studies were selected based on the inclusion and exclusion criteria. Most studies agreed that preoperative planning using DTI improves postoperative neuro-deficits, giving a greater resection yield and shortening the surgery time. The results also indicate that the re-evaluation of preoperative DTI intraoperatively assists in a better visualization of white matter tract shifts. Seven studies also suggested that DTI modified the surgical decision of the initial surgical approach and the rate of the GTR in tumor resection surgery. The utilization of DTI may give essential information on white matter tract pathways, for a better surgical approach, and eventually reduce the risk of neurologic deficits after surgery.

Awareness of Medical Doctors in Pusat Perubatan Universiti Kebangsaan Malaysia on Diagnostic Radiological Examination Related Radiation Exposure in the Pediatric Population.

BACKGROUND: When exposed to equal radiation doses, the risks for children and adolescents are more significant than for adults. Children grow quickly, and their cells are more sensitive to radiation. After radiation exposure, children have a higher risk of developing malignancies such as leukemia, thyroid abnormalities, and various types of cancers. The healthcare professionals' (in this context referring to medical doctors at all levels) awareness of imaging modalities associated with ionizing radiation is essential to ensure optimal patient management of cooperation in dealing with radiation exposure. Therefore, the present study is aimed to evaluate the awareness of healthcare professionals on medical imaging-related radiation exposure in the pediatric population in our center, Pusat Perubatan Universiti Kebangsaan Malaysia. MATERIALS AND METHODS: A cross-sectional survey was conducted among healthcare professionals using self-administered validated questionnaires in a university hospital for a duration of seven months. Healthcare professionals of all levels participated in this survey. RESULTS: A total of 145 healthcare professionals participated in this study. More than half of the respondents are house officers, 57.2% (n = 83). Results indicated that only 6 out of 145 healthcare professionals who participated in this survey had attended a radiation protection course. This survey showed that 37.2% of the respondents were unaware that chest radiographs would expose patients to ionizing radiation. Finally, results also indicated that senior doctors (21 out of 24 participants) showed better awareness of radiation protection knowledge. CONCLUSIONS: In general, healthcare professionals in our institution are inadequate in awareness of medical radiation exposure, particularly among house officers. However, the awareness of radiation safety and exposure improves with the number of years of clinical practice. We propose that some younger healthcare professionals do not take radiation safety seriously. Moreover, we would like to suggest all healthcare professionals must attend a radiation safety course, as we expect this will improve patient outcomes.

A Survey of Awareness of Parents and Caretakers on Diagnostic Radiological Examination Related Radiation Exposure in a Tertiary Hospital in Malaysia.

BACKGROUND: With the advancement in medical imaging, radiological application in the paediatric population has also increased. Children, generally more radiosensitive, have a higher risk of developing certain malignancies. Therefore, this may result in uneasiness among parents and caretakers when their children need to undergo medical imaging examination. Hence, this study aims to assess the awareness of parents' and caretakers' awareness of medical imaging-related radiation exposure in our institution and their opinion of a medical radiation exposure-tracking programme for the paediatric population. METHODOLOGY: A cross-sectional survey was conducted for 6 months duration among parents and caretakers, who brought their children (under 12 years old) for imaging. The questionnaire booklet had eleven knowledge-based questions to assess respondents on ionising radiation-associated medical imaging, the radiation-related risk and radiation safety precaution. RESULTS: Two hundred and fifteen respondents participated in this survey. More than 40% of the respondents failed to identify various dose-saving and ionising radiation-related imaging methods. Only 87 participants (40.5%) could correctly answer at least six out of eleven knowledge-based questions. Moreover, 88.4% of the respondents support a medical radiation exposure-tracking programme for their children. CONCLUSION: Parents and caretakers who visited our institution had inadequate awareness of medical radiation exposure. Appropriate measures need to be taken to address this promptly. Implementation of a medical radiation exposure-tracking programme for the paediatric population is considered timely as most respondents agree with this programme.

Diffusion tensor imaging indices as biomarkers for cognitive changes following paediatric radiotherapy: a systematic review and meta-analysis.

Diffusion tensor imaging (DTI) can detect subtle manifestations of white matter (WM) injury following paediatric radiotherapy, which may be a potential biomarker for cognitive changes. This study aimed to synthesise the relationships between DTI indices and cognitive changes following paediatric radiotherapy through systematic review and meta-analysis. PubMed and Scopus electronic databases were used to identify eligible studies. Quality assessment was performed using the National Institute of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Information on demographics, DTI changes, and associations to cognitive outcomes were extracted. Meta-analyses were performed on DTI changes in specific anatomical locations. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in the preparation of this report. Eighteen studies were included (median study size: 21; range 18-146). 17/18 studies showed significant cognitive decline following irradiation. Meta-analyses found significant cognitive changes within patient's group of acute lymphoblastic leukaemia (ALL; standard mean differences [SMD] = -0.075, P = 0.01) and brain tumours (BT; SMD = -1.037, P ≤ 0.001) compared to control/baseline. Both groups also had significantly lower fractional anisotropy (FA) scores in the corpus callosum (ALL: SMD = -0.979, P = 0.002; BT: SMD = -1.025, P < 0.001). Decreased FA was consistently associated with cognitive decline. Correlation on WMFA integrity to cognitive domains was statistically significant (Z = 9.86, P < 0.001) with a large effect size (r = 0.52). White matter tract integrity of the corpus callosum measured with FA has the potential to be a biomarker for radiotherapy-related cognitive decline. Inclusion of DTI in follow-up imaging should be encouraged.

Comparison of Mean Glandular Dose between Full-Field Digital Mammography and Digital Breast Tomosynthesis.

Early detection of breast cancer is diagnosed using mammography, the gold standard in breast screening. However, its increased use also provokes radiation-induced breast malignancy. Thus, monitoring and regulating the mean glandular dose (MGD) is essential. The purpose of this study was to determine MGD for full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) in the radiology department of a single centre. We also analysed the exposure factors as a function of breast thickness. A total of 436 patients underwent both FFDM and DBT. MGD was auto calculated by the mammographic machine for each projection. Patients' data included compressed breast thickness (CBT), peak kilovoltage (kVp), milliampere-seconds (mAs) and MGD (mGy). Result analysis showed that there is a significant difference in MGD between the two systems, namely FFDM and DBT. However, the MGD values in our centre were comparable to other centres, as well as the European guideline (<2.5 mGy) for a standard breast. Although DBT improves the clinical outcome and quality of diagnosis, the risk of radiation-induced carcinogenesis should not be neglected. Regular quality control testing on mammography equipment must be performed for dose monitoring in women following a screening mammography in the future.

The utilisation of resting-state fMRI as a pre-operative mapping tool in patients with brain tumours in comparison to task-based fMRI and intraoperative mapping: A systematic review.

PURPOSE: Resting-state functional Magnetic Resonance Imaging (rs-fMRI) is suggested to be a viable option for pre-operative mapping for patients with brain tumours. However, it remains an open issue whether the tool is useful in the clinical setting compared to task-based fMRI (T-fMRI) and intraoperative mapping. Thus, a systematic review was conducted to investigate the usefulness of this technique. METHODS: A systematic literature search of rs-fMRI methods applied as a pre-operative mapping tool was conducted using the PubMed/MEDLINE and Cochrane Library electronic databases following PRISMA guidelines. RESULTS: Results demonstrated that 50% (six out of twelve) of the studies comparing rs-fMRI and T-fMRI showed good concordance for both language and sensorimotor networks. In comparison to intraoperative mapping, 86% (six out of seven) studies found a good agreement to rs-fMRI. Finally, 87% (twenty out of twenty-three) studies agreed that rs-fMRI is a suitable and useful pre-operative mapping tool. CONCLUSIONS: rs-fMRI is a promising technique for pre-operative mapping in assessing the functional brain areas. However, the agreement between rs-fMRI with other techniques, including T-fMRI and intraoperative maps, is not yet optimal. Studies to ascertain and improve the sophistication in pre-processing of rs-fMRI imaging data are needed.

Neurocognitive impairment following proton therapy for paediatric brain tumour: a systematic review of post-therapy assessments.

BACKGROUND: Proton therapy (PT), frequently utilised to treat paediatric brain tumour (PBT) patients, eliminates exit dose and minimises dose to healthy tissues that theoretically can mitigate treatment-related effects including cognitive deficits. As clinical outcome data are emerging, we aimed to systematically review current evidence of cognitive changes following PT of PBT. MATERIALS AND METHODS: We searched PubMed and Scopus electronic databases to identify eligible reports on cognitive changes following PT of PBT according to PRISMA guidelines. Reports were extracted for information on demographics and cognitive outcomes. Then, they were systematically reviewed based on three themes: (1) comparison with photon therapy, (2) comparison with baseline cognitive measures, to population normative mean or radiotherapy-naïve PBT patients and (3) effects of dose distribution to cognition. RESULTS: Thirteen reports (median size (range): 70 (12-144)) were included. Four reports compared the cognitive outcome between PBT patients treated with proton to photon therapy and nine compared with baseline/normative mean/radiotherapy naïve from which two reported the effects of dose distribution. Reports found significantly poorer cognitive outcome among patients treated with photon therapy compared with proton therapy especially in general cognition and working memory. Craniospinal irradiation (CSI) was consistently associated with poorer cognitive outcome while focal therapy was associated with minor cognitive change/difference. In limited reports available, higher doses to the hippocampus and temporal lobes were implicated to larger cognitive change. CONCLUSION: Available evidence suggests that PT causes less cognitive deficits compared with photon therapy. Children who underwent focal therapy with proton were consistently shown to have low risk of cognitive deficit suggesting the need for future studies to separate them from CSI. Evidence on the effect of dose distribution to cognition in PT is yet to mature.

Study of common quantification methods of amide proton transfer magnetic resonance imaging for ischemic stroke detection.

PURPOSE: To assess the correlation and differences between common amide proton transfer (APT) quantification methods in the diagnosis of ischemic stroke. METHODS: Five APT quantification methods, including asymmetry analysis and its variants as well as two Lorentzian model-based methods, were applied to data acquired from six rats that underwent middle cerebral artery occlusion scanned at 9.4T. Diffusion and perfusion-weighted images, and water relaxation time maps were also acquired to study the relationship of these conventional imaging modalities with the different APT quantification methods. RESULTS: The APT ischemic area estimates had varying sizes (Jaccard index: 0.544 ≤ J ≤ 0.971) and had varying correlations in their distributions (Pearson correlation coefficient: 0.104 ≤ r ≤ 0.995), revealing discrepancies in the quantified ischemic areas. The Lorentzian methods produced the highest contrast-to-noise ratios (CNRs; 1.427 ≤ CNR ≤ 2.002), but generated APT ischemic areas that were comparable in size to the cerebral blood flow (CBF) deficit areas; asymmetry analysis and its variants produced APT ischemic areas that were smaller than the CBF deficit areas but larger than the apparent diffusion coefficient deficit areas, though having lower CNRs (0.561 ≤ CNR ≤ 1.083). CONCLUSION: There is a need to further investigate the accuracy and correlation of each quantification method with the pathophysiology using a larger scale multi-imaging modality and multi-time-point clinical study. Future studies should include the magnetization transfer ratio asymmetry results alongside the findings of the study to facilitate the comparison of results between different centers and also the published literature.

Utilization of functional MRI language paradigms for pre-operative mapping: a systematic review.

PURPOSE: Functional MRI (fMRI) can be employed to non-invasively localize brain regions involved in functional areas of language in patients with brain tumour, for applications including pre-operative mapping. The present systematic review was conducted to explore prevalence of different language paradigms utilised in conjunction with fMRI approaches for pre-operative mapping, with the aim of assessing their effectiveness and suitability. METHODS: A systematic literature search of brain tumours in the context of fMRI methods applied to pre-operative mapping for language functional areas was conducted using PubMed/MEDLINE and Scopus electronic database following PRISMA guidelines. The article search was conducted between the earliest record and March 1, 2019. References and citations were checked in Google Scholar database. RESULTS: Twenty-nine independent studies were identified, comprising 1031 adult participants with 976 patients characterised with different types and sizes of brain tumours, and the remaining 55 being healthy controls. These studies evaluated functional language areas in patients with brain tumours prior to surgical interventions using language-based fMRI. Results demonstrated that 86% of the studies used a Word Generation Task (WGT) to evoke functional language areas during pre-operative mapping. Fifty-seven percent of the studies that used language-based paradigms in conjunction with fMRI as a pre-operative mapping tool were in agreement with intra-operative results of language localization. CONCLUSIONS: WGT was most commonly utilised and is proposed as a suitable and useful technique for a language-based paradigm fMRI for pre-operative mapping. However, based on available evidence, WGT alone is not sufficient. We propose a combination and convergence paradigms for a more sensitive and specific map of language function for pre-operative mapping. A standard guideline for clinical applications should be established.