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Background Impaired glucose metabolism is characteristic of several types of dementia, preceding cognitive symptoms and structural brain changes. Reduced glucose uptake in specific brain regions, detected using fluorine 18 (18F) fluorodeoxyglucose (FDG) PET, is a valuable diagnostic marker in Alzheimer disease (AD). However, the use of 18F-FDG PET in clinical practice may be limited by equipment availability and high cost. Purpose To test the feasibility of using MRI-based deuterium (2H) metabolic imaging (DMI) at a clinical magnetic field strength (3 T) to detect and localize changes in the concentration of glucose and its metabolites in the brains of patients with a clinical diagnosis of AD. Materials and Methods Participants were recruited for this prospective case-control pilot study between March 2021 and February 2023. DMI was performed at 3 T using a custom birdcage head coil following oral administration of deuterium-labeled glucose (0.75 g/kg). Unlocalized whole-brain MR spectroscopy (MRS) and three-dimensional MR spectroscopic imaging (MRSI) (voxel size, 3.2 cm cubic) were performed. Ratios of 2H-glucose, 2H-glutamate and 2H-glutamine (2H-Glx), and 2H-lactate spectroscopic peak signals to 2H-water peak signal were calculated for the whole-brain MR spectra and for individual MRSI voxels. Results A total of 19 participants, including 10 participants with AD (mean age, 68 years ± 5 [SD]; eight males) and nine cognitively healthy control participants (mean age, 70 years ± 6; six males) were evaluated. Whole-brain spectra demonstrated a reduced ratio of 2H-Glx to 2H-glucose peak signals in participants with AD compared with control participants (0.41 ± 0.09 vs 0.58 ± 0.20, respectively; P = .04), suggesting an impairment of oxidative glucose metabolism in AD. However, there was no evidence of localization of these changes to the expected regions of metabolic impairment at MRSI, presumably due to insufficient spatial resolution. Conclusion DMI at 3 T demonstrated impairment of oxidative glucose metabolism in the brains of patients with AD but no evidence of regional signal differences. © RSNA, 2024 Supplemental material is available for this article.
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Doença de Alzheimer , Encéfalo , Deutério , Imageamento por Ressonância Magnética , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Projetos Piloto , Masculino , Feminino , Estudos de Casos e Controles , Idoso , Estudos Prospectivos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Glucose/metabolismo , Pessoa de Meia-Idade , Estudos de Viabilidade , Idoso de 80 Anos ou maisRESUMO
Neuroferritinopathy is a disorder of neurodegeneration with brain iron accumulation that has no proven disease-modifying treatments. Clinical trials require biomarkers of iron deposition. We examined brain iron accumulation in one presymptomatic FTL mutation carrier, two individuals with neuroferritinopathy and one healthy control using ultra-high-field 7T MRI. There was increased magnetic susceptibility, suggestive of iron deposition, in superficial and deep gray matter in both presymptomatic and symptomatic neuroferritinopathy. Cavitation of the putamen and globus pallidus increased with disease stage and at follow up. The widespread brain iron deposition in presymptomatic and early disease provides an opportunity for monitoring disease-modifying intervention.
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Distúrbios do Metabolismo do Ferro , Ferro , Imageamento por Ressonância Magnética , Distrofias Neuroaxonais , Humanos , Distrofias Neuroaxonais/diagnóstico por imagem , Distrofias Neuroaxonais/genética , Distrofias Neuroaxonais/metabolismo , Distrofias Neuroaxonais/patologia , Distúrbios do Metabolismo do Ferro/diagnóstico por imagem , Distúrbios do Metabolismo do Ferro/metabolismo , Distúrbios do Metabolismo do Ferro/genética , Ferro/metabolismo , Adulto , Masculino , Feminino , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Pessoa de Meia-Idade , Apoferritinas/metabolismo , Apoferritinas/genéticaRESUMO
BACKGROUND: Improving intraoperative accuracy with a validated surgical biomarker is important because identifying high-grade areas within a glioma will aid neurosurgical decision-making and sampling. METHODS: We designed a multicentre, prospective surgical cohort study (GALA-BIDD) to validate the presence of visible fluorescence as a pragmatic intraoperative surgical biomarker of suspected high-grade disease within a tumour mass in patients undergoing 5-aminolevulinic acid (5-ALA) fluorescence-guided cytoreductive surgery. RESULTS: A total of 106 patients with a suspected high-grade glioma or malignant transformation of a low-grade glioma were enrolled. Among the 99 patients who received 5-ALA, 89 patients were eligible to assess the correlation of fluorescence with diagnosis as per protocol. Of these 89, 81 patients had visible fluorescence at surgery, and 8 patients had no fluorescence. A total of 80 out of 81 fluorescent patients were diagnosed as high-grade gliomas on postoperative central review with 1 low-grade glioma case. Among the eight patients given 5-ALA who did not show any visible fluorescence, none were high-grade gliomas, and all were low-grade gliomas. Of the seven patients suspected radiologically of malignant transformation of low-grade gliomas and with visible fluorescence at surgery, six were diagnosed with high-grade gliomas, and one had no tissue collected. CONCLUSION: In patients where there is clinical suspicion, visible 5-ALA fluorescence has clinical utility as an intraoperative surgical biomarker of high-grade gliomas and can aid surgical decision-making and sampling. Further studies assessing the use of 5-ALA to assess malignant transformation in all diffuse gliomas may be valuable.
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Glioblastoma is characterized by diffuse infiltration into the surrounding tissue along white matter tracts. Identifying the invisible tumour invasion beyond focal lesion promises more effective treatment, which remains a significant challenge. It is increasingly accepted that glioblastoma could widely affect brain structure and function, and further lead to reorganization of neural connectivity. Quantifying neural connectivity in glioblastoma may provide a valuable tool for identifying tumour invasion. Here we propose an approach to systematically identify tumour invasion by quantifying the structural connectome in glioblastoma patients. We first recruit two independent prospective glioblastoma cohorts: the discovery cohort with 117 patients and validation cohort with 42 patients. Next, we use diffusion MRI of healthy subjects to construct tractography templates indicating white matter connection pathways between brain regions. Next, we construct fractional anisotropy skeletons from diffusion MRI using an improved voxel projection approach based on the tract-based spatial statistics, where the strengths of white matter connection and brain regions are estimated. To quantify the disrupted connectome, we calculate the deviation of the connectome strengths of patients from that of the age-matched healthy controls. We then categorize the disruption into regional disruptions on the basis of the relative location of connectome to focal lesions. We also characterize the topological properties of the patient connectome based on the graph theory. Finally, we investigate the clinical, cognitive and prognostic significance of connectome metrics using Pearson correlation test, mediation test and survival models. Our results show that the connectome disruptions in glioblastoma patients are widespread in the normal-appearing brain beyond focal lesions, associated with lower preoperative performance (P < 0.001), impaired cognitive function (P < 0.001) and worse survival (overall survival: hazard ratio = 1.46, P = 0.049; progression-free survival: hazard ratio = 1.49, P = 0.019). Additionally, these distant disruptions mediate the effect on topological alterations of the connectome (mediation effect: clustering coefficient -0.017, P < 0.001, characteristic path length 0.17, P = 0.008). Further, the preserved connectome in the normal-appearing brain demonstrates evidence of connectivity reorganization, where the increased neural connectivity is associated with better overall survival (log-rank P = 0.005). In conclusion, our connectome approach could reveal and quantify the glioblastoma invasion distant from the focal lesion and invisible on the conventional MRI. The structural disruptions in the normal-appearing brain were associated with the topological alteration of the brain and could indicate treatment target. Our approach promises to aid more accurate patient stratification and more precise treatment planning.
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Conectoma , Glioblastoma , Substância Branca , Humanos , Conectoma/métodos , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Imagem de Tensor de Difusão/métodos , Estudos Prospectivos , Encéfalo/patologia , Substância Branca/patologiaRESUMO
BACKGROUND: Resorbable hemostatic agents left behind postoperatively occasionally result in granulomatous space-occupying lesions known as "gossypibomas." The authors report a case of an intracranial gossypiboma, which is exceedingly rare and frequently radiologically indistinguishable from other lesions. OBSERVATIONS: A 35-year-old woman presented with a generalized tonic-clonic seizure and subsequent left-sided hemiparesis. Magnetic resonance imaging showed an enhancing lobulated lesion subjacent to a right frontal burr hole, surrounded by vasogenic edema with mass effect and midline shift. Nine years earlier, she had had a triple bolt inserted to monitor intracranial pressure after sustaining a traumatic brain injury. Surgicel was used to control bleeding during insertion. Colocation of the lesion with the position of triple bolt 9 years earlier raised suspicion for gossypiboma. However, the minor nature of the surgery and the length of time since surgery to presentation placed this case well outside the range of cases reported in the literature. The lesion was resected en bloc with no recurrence 18 months later. Histological examination revealed the presence of foreign material. However, given its minute size, confirming its nature was not possible. Lessons: The authors show that gossypibomas can occur following a relatively minor procedure and remain clinically and radiologically silent for much longer than previously reported.
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Deviations in laboratory tests assessing liver function in patients with COVID-19 are frequently observed. Their importance and pathogenesis are still debated. In our retrospective study, we analyzed liver-related parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), total bilirubin (TBIL), albumin, comorbidities and other selected potential risk factors in patients admitted with SARS-CoV-2 infection to assess their prognostic value for intensive care unit admission, mechanical ventilation necessity and mortality. We compared the prognostic effectiveness of these parameters separately and in pairs to the neutrophil-to-lymphocyte ratio (NLR) as an independent risk factor of in-hospital mortality, using the Akaike Information Criterion (AIC). Data were collected from 2109 included patients. We created models using a sample with complete laboratory tests n = 401 and then applied them to the whole studied group excluding patients with missing singular variables. We estimated that albumin may be a better predictor of the COVID-19-severity course compared to NLR, irrespective of comorbidities (p < 0.001). Additionally, we determined that hypoalbuminemia in combination with AST (OR 1.003, p = 0.008) or TBIL (OR 1.657, p = 0.001) creates excellent prediction models for in-hospital mortality. In conclusion, the early evaluation of albumin levels and liver-related parameters may be indispensable tools for the early assessment of the clinical course of patients with COVID-19.
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BACKGROUND: Even though coronary artery disease (CAD) is considered an independent risk factor of an unfavorable outcome of SARS-CoV-2-infection, the clinical course of COVID-19 in subjects with CAD is heterogeneous, ranging from clinically asymptomatic to fatal cases. Since the individual C2HEST components are similar to the COVID-19 risk factors, we evaluated its predictive value in CAD subjects. MATERIALS AND METHODS: In total, 2183 patients hospitalized due to confirmed COVID-19 were enrolled onto this study consecutively. Based on past medical history, subjects were assigned to one of two of the study arms (CAD vs. non-CAD) and allocated to different risk strata, based on the C2HEST score. RESULTS: The CAD cohort included 228 subjects, while the non-CAD cohort consisted of 1956 patients. In-hospital, 3-month and 6-month mortality was highest in the high-risk C2HEST stratum in the CAD cohort, reaching 43.06%, 56.25% and 65.89%, respectively, whereas in the non-CAD cohort in the high-risk stratum, it reached: 26.92%, 50.77% and 64.55%. Significant differences in mortality between the C2HEST stratum in the CAD arm were observed in post hoc analysis only for medium- vs. high-risk strata. The C2HEST score in the CAD cohort could predict hypovolemic shock, pneumonia and acute heart failure during hospitalization, whereas in the non-CAD cohort, it could predict cardiovascular events (myocardial injury, acute heart failure, myocardial infract, carcinogenic shock), pneumonia, acute liver dysfunction and renal injury as well as bleedings. CONCLUSIONS: The C2HEST score is a simple, easy-to-apply tool which might be useful in risk stratification, preferably in non-CAD subjects admitted to hospital due to COVID-19.
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COVID-19 , Doença da Artéria Coronariana , Insuficiência Cardíaca , COVID-19/diagnóstico , Doença da Artéria Coronariana/diagnóstico , Hospitalização , Humanos , Medição de Risco , Fatores de Risco , SARS-CoV-2RESUMO
Purpose To evaluate glioblastoma (GBM) metabolism by using hyperpolarized carbon 13 (13C) MRI to monitor the exchange of the hyperpolarized 13C label between injected [1-13C]pyruvate and tumor lactate and bicarbonate. Materials and Methods In this prospective study, seven treatment-naive patients (age [mean ± SD], 60 years ± 11; five men) with GBM were imaged at 3 T by using a dual-tuned 13C-hydrogen 1 head coil. Hyperpolarized [1-13C]pyruvate was injected, and signal was acquired by using a dynamic MRI spiral sequence. Metabolism was assessed within the tumor, in the normal-appearing brain parenchyma (NABP), and in healthy volunteers by using paired or unpaired t tests and a Wilcoxon signed rank test. The Spearman ρ correlation coefficient was used to correlate metabolite labeling with lactate dehydrogenase A (LDH-A) expression and some immunohistochemical markers. The Benjamini-Hochberg procedure was used to correct for multiple comparisons. Results The bicarbonate-to-pyruvate (BP) ratio was lower in the tumor than in the contralateral NABP (P < .01). The tumor lactate-to-pyruvate (LP) ratio was not different from that in the NABP (P = .38). The LP and BP ratios in the NABP were higher than those observed previously in healthy volunteers (P < .05). Tumor lactate and bicarbonate signal intensities were strongly correlated with the pyruvate signal intensity (ρ = 0.92, P < .001, and ρ = 0.66, P < .001, respectively), and the LP ratio was weakly correlated with LDH-A expression in biopsy samples (ρ = 0.43, P = .04). Conclusion Hyperpolarized 13C MRI demonstrated variation in lactate labeling in GBM, both within and between tumors. In contrast, bicarbonate labeling was consistently lower in tumors than in the surrounding NABP. Keywords: Hyperpolarized 13C MRI, Glioblastoma, Metabolism, Cancer, MRI, Neuro-oncology Supplemental material is available for this article. Published under a CC BY 4.0 license.
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Glioblastoma , Bicarbonatos , Glioblastoma/diagnóstico por imagem , Humanos , Lactato Desidrogenase 5 , Ácido Láctico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ácido Pirúvico/metabolismoRESUMO
A thorough understanding of the skull anatomy is of key importance to radiologists as well as specialist physicians and surgeons. We describe the anatomy of the neurocranium comprising calvaria (the skull vault) and the skull base and discuss the most common and clinically relevant anatomic variants.
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Base do Crânio , Crânio , Humanos , Crânio/anatomia & histologia , Crânio/diagnóstico por imagem , Base do Crânio/diagnóstico por imagem , Base do Crânio/cirurgiaRESUMO
Background: Patients with heart failure represent a vulnerable population for COVID-19 and are prone to having worse prognoses and higher fatality rates. Still, the clinical course of the infection is dynamic, and complication occurrence in particular in patients with heart failure is fairly unpredictable. Considering that individual components of the C2HEST (C2: Coronary Artery Diseases (CAD)/Chronic obstructive pulmonary disease (COPD); H: Hypertension; E: Elderly (Age ≥ 75); S: Systolic HF; T: Thyroid disease) are parallel to COVID-19 mortality risk factors, we evaluate the predictive value of C2HEST score in patients with heart failure (HF) Material and Methods: The retrospective medical data analysis of 2184 COVID-19 patients hospitalized in the University Hospital in Wroclaw between February 2020 and June 2021 was the basis of the study. The measured outcomes included: in-hospital mortality, 3-month and 6-month all-cause-mortality, non-fatal end of hospitalization, and adverse in-hospital clinical events. Results: The heart failure cohort consists of 255 patients, while 1929 patients were assigned to the non-HF cohort. The in-hospital, 3-month, and 6-month mortality rates were highest in the HF cohort high-risk C2HEST stratum, reaching 38.61%, 53.96%, and 65.36%, respectively. In the non-HF cohort, in-hospital, 3-month, and 6-month mortalities were also highest in the high-risk C2HEST stratum and came to 26.39%, 52.78%, and 65.0%, respectively. An additional point in the C2HEST score increased the total death intensity in 10% of HF subjects (HR 1.100, 95% CI 0.968−1.250 p = 0.143) while in the non-HF cohort, the same value increased by 62.3% (HR 1.623, 95% CI 1.518−1.734 p < 0.0001). Conclusions: The C2HEST score risk in the HF cohort failed to show discriminatory performance in terms of mortality and other clinical adverse outcomes during hospitalization. C2HEST score in the non-HF cohort showed significantly better performance in terms of predicting in-hospital and 6-month mortality and other non-fatal clinical outcomes such as cardiovascular events (myocardial injury, acute heart failure, myocardial infarction, cardiogenic shock), pneumonia, sepsis, and acute renal injury.
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Deuterium metabolic imaging (DMI) and hyperpolarized 13C-pyruvate MRI (13C-HPMRI) are two emerging methods for non-invasive and non-ionizing imaging of tissue metabolism. Imaging cerebral metabolism has potential applications in cancer, neurodegeneration, multiple sclerosis, traumatic brain injury, stroke, and inborn errors of metabolism. Here we directly compare these two non-invasive methods at 3 T for the first time in humans and show how they simultaneously probe both oxidative and non-oxidative metabolism. DMI was undertaken 1-2 h after oral administration of [6,6'-2H2]glucose, and 13C-MRI was performed immediately following intravenous injection of hyperpolarized [1-13C]pyruvate in ten and nine normal volunteers within each arm respectively. DMI was used to generate maps of deuterium-labelled water, glucose, lactate, and glutamate/glutamine (Glx) and the spectral separation demonstrated that DMI is feasible at 3 T. 13C-HPMRI generated maps of hyperpolarized carbon-13 labelled pyruvate, lactate, and bicarbonate. The ratio of 13C-lactate/13C-bicarbonate (mean 3.7 ± 1.2) acquired with 13C-HPMRI was higher than the equivalent 2H-lactate/2H-Glx ratio (mean 0.18 ± 0.09) acquired using DMI. These differences can be explained by the route of administering each probe, the timing of imaging after ingestion or injection, as well as the biological differences in cerebral uptake and cellular physiology between the two molecules. The results demonstrate these two metabolic imaging methods provide different yet complementary readouts of oxidative and reductive metabolism within a clinically feasible timescale. Furthermore, as DMI was undertaken at a clinical field strength within a ten-minute scan time, it demonstrates its potential as a routine clinical tool in the future.
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Bicarbonatos , Imageamento por Ressonância Magnética , Bicarbonatos/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Isótopos de Carbono/metabolismo , Deutério/metabolismo , Glucose/metabolismo , Humanos , Ácido Láctico/metabolismo , Imageamento por Ressonância Magnética/métodos , Ácido PirúvicoRESUMO
Background: Since the outbreak of the COVID-19 pandemic, a growing number of evidence suggests that COVID-19 presents sex-dependent differences in clinical course and outcomes. Nevertheless, there is still an unmet need to stratify the risk for poor outcome at the beginning of hospitalization. Since individual C2HEST components are similar COVID-19 mortality risk factors, we evaluated sex-related predictive value of the score. Material and Methods: A total of 2183 medical records of consecutive patients hospitalized due to confirmed SARS-CoV-2 infections were analyzed. Subjects were assigned to one of two of the study arms (male vs. female) and afterward allocated to different stratum based on the C2HEST score result. The measured outcomes included: in-hospital-mortality, three-month- and six-month-all-cause-mortality and in-hospital non-fatal adverse clinical events. Results: The C2HEST score predicted the mortality with better sensitivity in female population regarding the short- and mid-term. Among secondary outcomes, C2HEST-score revealed predictive value in both genders for pneumonia, myocardial injury, myocardial infarction, acute heart failure, cardiogenic shock, and acute kidney injury. Additionally in the male cohort, the C2HEST value predicted acute liver dysfunction and all-cause bleeding, whereas in the female arm-stroke/TIA and SIRS. Conclusion: In the present study, we demonstrated the better C2HEST-score predictive value for mortality in women and illustrated sex-dependent differences predicting non-fatal secondary outcomes.
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COVID-19 , Feminino , Humanos , Masculino , Pandemias , Prognóstico , Estudos Retrospectivos , Medição de Risco , SARS-CoV-2RESUMO
BACKGROUND: Diabetes mellitus is among the most frequent comorbidities worsening COVID-19 outcome. Nevertheless, there are no data regarding the optimal risk stratification of patients with diabetes and COVID-19. Since individual C2HEST components reflect the comorbidities, we assumed that the score could predict COVID-19 outcomes. MATERIAL AND METHODS: A total of 2184 medical records of patients hospitalized for COVID-19 at the medical university center were analyzed, including 473 diabetic patients and 1666 patients without any glucose or metabolic abnormalities. The variables of patients' baseline characteristics were retrieved to calculate the C2HEST score and subsequently the diabetic and non-diabetic subjects were assigned to the following categories: low-, medium- or high-risk. The measured outcomes included: in-hospital mortality; 3-month and 6-month all-cause mortality; non-fatal end of hospitalization (discharged home/sudden-deterioration/rehabilitation) and adverse in-hospital clinical events. RESULTS: A total of 194 deaths (41%) were reported in the diabetic cohort, including 115 in-hospital deaths (24.3%). The 3-month and 6-month in-hospital mortality was highest in the high-risk C2HEST stratum. The C2HEST score revealed to be more sensitive in non-diabetic-group. The estimated six-month survival probability for high-risk subjects reached 0.4 in both cohorts whereas for the low-risk group, the six-month survival probability was 0.7 in the diabetic vs. 0.85 in the non-diabetic group-levels which were maintained during whole observation period. In both cohorts, receiver operating characteristics revealed that C2HEST predicts the following: cardiogenic shock; acute heart failure; myocardial injury; and in-hospital acute kidney injury. CONCLUSIONS: We demonstrated the usefulness and performance of the C2HEST score in predicting the adverse COVID-19 outcomes in hospitalized diabetic subjects.
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Senility has been identified among the strongest risk predictors for unfavorable COVID-19-outcome. However, even in the elderly population, the clinical course of infection in individual patients remains unpredictable. Hence, there is an urgent need for developing a simple tool predicting adverse COVID-19-outcomes. We assumed that the C2HEST-score could predict unfavorable clinical outcomes in the elderly subjects with COVID-19-subjects. METHODS: We retrospectively analyzed 1047 medical records of patients at age > 65 years, hospitalized at the medical university center due to COVID-19. Subsequently, patients were divided into three categories depending on their C2HEST-score result. RESULTS: We noticed significant differences in the in-hospital and 3-month and 6-month mortality-which was the highest in high-risk-C2HEST-stratum reaching 35.7%, 54.4%, and 65.9%, respectively. The medium-risk-stratum mortalities reached 24.1% 43.4%, and 57.6% and for low-risk-stratum 14.4%, 25.8%, and 39.2% respectively. In the C2HEST-score model, a change from the low to the medium category increased the probability of death intensity approximately two-times. Subsequently, transfer from the low-risk to the high-risk-stratum raised all-cause-death-intensity 2.7-times. Analysis of the secondary outcomes revealed that the C2HEST-score has predictive value for acute kidney injury, acute heart failure, and cardiogenic shock. CONCLUSIONS: C2HEST-score analysis on admission to the hospital may predict the mortality, acute kidney injury, and acute heart failure in elderly subjects with COVID-19.
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The coronavirus disease 2019 (COVID-19) shows high incidence of thromboembolic events in humans. In the present study, we aimed to evaluate if anticoagulation prior to COVID-19 infection may impact clinical profile, as well as mortality rate among patients hospitalized with COVID-19. The study was based on retrospective analysis of medical records of patients with laboratory confirmed SARS-CoV-2 infection. After propensity score matching (PSM), a group of 236 patients receiving any anticoagulant treatment prior to COVID-19 infection (AT group) was compared to 236 patients without previous anticoagulation (no AT group). In 180 days, the observation we noted comparable mortality rate in AT and no AT groups (38.5% vs. 41.1%, p = 0.51). Similarly, we did not observe any statistically significant differences in admission in the intensive care unit (14.1% vs. 9.6%, p = 0.20), intubation and mechanical ventilation (15.0% vs. 11.6%, p = 0.38), catecholamines usage (14.3% vs. 13.8%, p = 0.86), and bleeding rate (6.3% vs. 8.9%, p = 0.37) in both groups. Our results suggest that antithrombotic treatment prior to COVID-19 infection is unlikely to be protective for morbidity and mortality in patients hospitalized with COVID-19.
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Conservadores da Densidade Óssea/efeitos adversos , Denosumab/efeitos adversos , Ácido Ibandrônico/efeitos adversos , Arcada Osseodentária/diagnóstico por imagem , Osteonecrose/induzido quimicamente , Osteonecrose/complicações , Idoso , Feminino , Humanos , Osteonecrose/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodosRESUMO
Background Glioblastoma (GBM) is the commonest primary malignant brain tumour in adults and effective treatment options are limited. Combining local chemotherapy with enhanced surgical resection using 5-aminolevulinic acid (5-ALA) could improve outcomes. Here we assess the safety and feasibility of combining BCNU wafers with 5-ALA-guided surgery. Methods We conducted a multicentre feasibility study of 5-ALA with BCNU wafers followed by standard-of-care chemoradiotherapy (chemoRT) in patients with suspected GBM. Patients judged suitable for radical resection were administered 5-ALA pre-operatively and BCNU wafers at the end resection. Post-operative treatment continued as per routine clinical practice. The primary objective was to establish if combining 5-ALA and BCNU wafers is safe without compromising patients from receiving standard chemoRT. Results Seventy-two patients were recruited, sixty-four (88.9%) received BCNU wafer implants, and fifty-nine (81.9%) patients remained eligible following formal histological diagnosis. Seven (11.9%) eligible patients suffered surgical complications but only two (3.4%) were not able to begin chemoRT, four (6.8%) additional patients did not begin chemoRT within 6 weeks of surgery due to surgical complications. Eleven (18.6%) patients did not begin chemoRT for other reasons (other toxicity (n = 3), death (n = 3), lost to follow-up/withdrew (n = 3), clinical decision (n = 1), poor performance status (n = 1)). Median progression-free survival was 8.7 months (95% CI: 6.4-9.8) and median overall survival was 14.7 months (95% CI: 11.7-16.8). Conclusions Combining BCNU wafers with 5-ALA-guided surgery in newly diagnosed GBM patients is both feasible and tolerable in terms of surgical morbidity and overall toxicity. Any potential therapeutic benefit for the sequential use of 5-ALA and BCNU with chemoRT requires further investigation with improved local delivery technologies.
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Measurements of water diffusion with MRI have been used as a biomarker of tissue microstructure and heterogeneity. In this study, diffusion kurtosis tensor imaging (DKTI) of the brain was undertaken in 10 healthy volunteers at a clinical field strength of 3 T. Diffusion and kurtosis metrics were measured in regions-of-interest on the resulting maps and compared with quantitative analysis of normal post-mortem tissue histology from separate age-matched donors. White matter regions showed low diffusion (0.60 ± 0.04 × 10-3 mm2/s) and high kurtosis (1.17 ± 0.06), consistent with a structured heterogeneous environment comprising parallel neuronal fibres. Grey matter showed intermediate diffusion (0.80 ± 0.02 × 10-3 mm2/s) and kurtosis (0.82 ± 0.05) values. An important finding is that the subcortical regions investigated (thalamus, caudate and putamen) showed similar diffusion and kurtosis properties to white matter. Histological staining of the subcortical nuclei demonstrated that the predominant grey matter was permeated by small white matter bundles, which could account for the similar kurtosis to white matter. Quantitative histological analysis demonstrated higher mean tissue kurtosis and vector standard deviation values for white matter (1.08 and 0.81) compared to the subcortical regions (0.34 and 0.59). Mean diffusion on DKTI was positively correlated with tissue kurtosis (r = 0.82, p < 0.05) and negatively correlated with vector standard deviation (r = -0.69, p < 0.05). This study demonstrates how DKTI can be used to study regional structural variations in the cerebral tissue microenvironment and could be used to probe microstructural changes within diseased tissue in the future.
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Encéfalo/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Magnetic resonance fingerprinting (MRF) is highly promising as a quantitative MRI technique due to its accuracy, robustness, and efficiency. Previous studies have found high repeatability and reproducibility of 2D MRF acquisitions in the brain. Here, we have extended our investigations to 3D MRF acquisitions covering the whole brain using spiral projection k-space trajectories. Our travelling head study acquired test/retest data from the brains of 12 healthy volunteers and 8 MRI systems (3 systems at 3 T and 5 at 1.5 T, all from a single vendor), using a study design not requiring all subjects to be scanned at all sites. The pulse sequence and reconstruction algorithm were the same for all acquisitions. After registration of the MRF-derived PD T1 and T2 maps to an anatomical atlas, coefficients of variation (CVs) were computed to assess test/retest repeatability and inter-site reproducibility in each voxel, while a General Linear Model (GLM) was used to determine the voxel-wise variability between all confounders, which included test/retest, subject, field strength and site. Our analysis demonstrated a high repeatability (CVs 0.7-1.3% for T1, 2.0-7.8% for T2, 1.4-2.5% for normalized PD) and reproducibility (CVs of 2.0-5.8% for T1, 7.4-10.2% for T2, 5.2-9.2% for normalized PD) in gray and white matter. Both repeatability and reproducibility improved when compared to similar experiments using 2D acquisitions. Three-dimensional MRF obtains highly repeatable and reproducible estimations of T1 and T2, supporting the translation of MRF-based fast quantitative imaging into clinical applications.
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Encéfalo/diagnóstico por imagem , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Adulto , Feminino , Voluntários Saudáveis , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Reprodutibilidade dos TestesRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.