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1.
NMR Biomed ; 37(5): e5101, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38303627

RESUMO

1H-magnetic resonance spectroscopy (MRS) has the potential to improve the noninvasive diagnostic accuracy for paediatric brain tumours. However, studies analysing large, comprehensive, multicentre datasets are lacking, hindering translation to widespread clinical practice. Single-voxel MRS (point-resolved single-voxel spectroscopy sequence, 1.5 T: echo time [TE] 23-37 ms/135-144 ms, repetition time [TR] 1500 ms; 3 T: TE 37-41 ms/135-144 ms, TR 2000 ms) was performed from 2003 to 2012 during routine magnetic resonance imaging for a suspected brain tumour on 340 children from five hospitals with 464 spectra being available for analysis and 281 meeting quality control. Mean spectra were generated for 13 tumour types. Mann-Whitney U-tests and Kruskal-Wallis tests were used to compare mean metabolite concentrations. Receiver operator characteristic curves were used to determine the potential for individual metabolites to discriminate between specific tumour types. Principal component analysis followed by linear discriminant analysis was used to construct a classifier to discriminate the three main central nervous system tumour types in paediatrics. Mean concentrations of metabolites were shown to differ significantly between tumour types. Large variability existed across each tumour type, but individual metabolites were able to aid discrimination between some tumour types of importance. Complete metabolite profiles were found to be strongly characteristic of tumour type and, when combined with the machine learning methods, demonstrated a diagnostic accuracy of 93% for distinguishing between the three main tumour groups (medulloblastoma, pilocytic astrocytoma and ependymoma). The accuracy of this approach was similar even when data of marginal quality were included, greatly reducing the proportion of MRS excluded for poor quality. Children's brain tumours are strongly characterised by MRS metabolite profiles readily acquired during routine clinical practice, and this information can be used to support noninvasive diagnosis. This study provides both key evidence and an important resource for the future use of MRS in the diagnosis of children's brain tumours.


Assuntos
Biomarcadores Tumorais , Neoplasias Encefálicas , Humanos , Criança , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Imageamento por Ressonância Magnética
2.
J Med Genet ; 57(4): 226-236, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31719169

RESUMO

BACKGROUND: Germline TP53 gene pathogenic variants (pv) cause a very high lifetime risk of developing cancer, almost 100% for women and 75% for men. In the UK, annual MRI breast screening is recommended for female TP53 pv carriers. The SIGNIFY study (Magnetic Resonance Imaging screening in Li Fraumeni syndrome: An exploratory whole body MRI) study reported outcomes of whole-body MRI (WB-MRI) in a cohort of 44 TP53 pv carriers and 44 matched population controls. The results supported the use of a baseline WB-MRI screen in all adult TP53 pv carriers. Here we report the acceptability of WB-MRI screening and effects on psychosocial functioning and health-related quality of life in the short and medium terms. METHODS: Psychosocial and other assessments were carried out at study enrolment, immediately before MRI, before and after MRI results, and at 12, 26 and 52 weeks' follow-up. RESULTS: WB-MRI was found to be acceptable with high levels of satisfaction and low levels of psychological morbidity throughout. Although their mean levels of cancer worry were not high, carriers had significantly more cancer worry at most time-points than controls. They also reported significantly more clinically significant intrusive and avoidant thoughts about cancer than controls at all time-points. There were no clinically significant adverse psychosocial outcomes in either carriers with a history of cancer or in those requiring further investigations. CONCLUSION: WB-MRI screening can be implemented in TP53 pv carriers without adverse psychosocial outcomes in the short and medium terms. A previous cancer diagnosis may predict a better psychosocial outcome. Some carriers seriously underestimate their risk of cancer. Carriers of pv should have access to a clinician to help them develop adaptive strategies to cope with cancer-related concerns and respond to clinically significant depression and/or anxiety.


Assuntos
Síndrome de Li-Fraumeni/diagnóstico , Imageamento por Ressonância Magnética , Neoplasias/diagnóstico , Proteína Supressora de Tumor p53/genética , Adulto , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa/genética , Heterozigoto , Humanos , Síndrome de Li-Fraumeni/diagnóstico por imagem , Síndrome de Li-Fraumeni/genética , Síndrome de Li-Fraumeni/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico por imagem , Neoplasias/genética , Neoplasias/patologia , Fatores de Risco , Imagem Corporal Total , Adulto Jovem
3.
Br J Cancer ; 122(1): 72-81, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31819183

RESUMO

BACKGROUND: BRAF inhibitors, such as vemurafenib, have shown efficacy in BRAF-mutant melanoma treatment but acquired-resistance invariably develops. Unveiling the potential vulnerabilities associated with vemurafenib resistance could provide rational strategies for combinatorial treatment. METHODS: This work investigates the metabolic characteristics and vulnerabilities of acquired resistance to vemurafenib in three generated BRAF-mutant human melanoma cell clones, analysing metabolic profiles, gene and protein expression in baseline and nutrient withdrawal conditions. Preclinical findings are correlated with gene expression analysis from publicly available clinical datasets. RESULTS: Two vemurafenib-resistant clones showed dependency on lipid metabolism and increased prostaglandin E2 synthesis and were more responsive to vemurafenib under EGFR inhibition, potentially implicating inflammatory lipid and EGFR signalling in ERK reactivation and vemurafenib resistance. The third resistant clone showed higher pyruvate-carboxylase (PC) activity indicating increased anaplerotic mitochondrial metabolism, concomitant with reduced GLUT-1, increased PC protein expression and survival advantage under nutrient-depleted conditions. Prostaglandin synthase (PTGES) expression was inversely correlated with melanoma patient survival. Increases in PC and PTGES gene expression were observed in some patients following progression on BRAF inhibitors. CONCLUSIONS: Altogether, our data highlight heterogeneity in metabolic adaptations during acquired resistance to vemurafenib in BRAF-mutant melanoma, potentially uncovering key clinically-relevant mechanisms for combinatorial therapeutic targeting.


Assuntos
Antineoplásicos/farmacologia , Dinoprostona/biossíntese , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Melanoma/metabolismo , Mitocôndrias/metabolismo , Mutação , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/metabolismo , Vemurafenib/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Gefitinibe/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Melanoma/patologia , Mitocôndrias/efeitos dos fármacos , Prostaglandina-E Sintases/genética , Piruvato Carboxilase/genética , Transdução de Sinais/efeitos dos fármacos , Neoplasias Cutâneas/patologia
4.
Br J Cancer ; 122(6): 895-903, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31937921

RESUMO

BACKGROUND: Monocarboxylate transporter 1 (MCT1) is a regulator of cell metabolism and a therapeutic target for cancer treatment. Understanding the changes in tumour function accompanying MCT1 inhibition will better characterise the anti-tumour effects of MCT1 inhibitors, potentially enabling the identification of pharmacodynamic biomarkers for the clinical development of these agents. METHODS: We assessed the impact of the MCT1 inhibitor AZD3965 on tumour metabolism and immune cell infiltration as key determinants of tumour biological function in the MCT1-dependent Raji B cell lymphoma model. RESULTS: Treatment of Raji xenograft-bearing severe combined immunodeficiency mice with AZD3965 led to inhibition of tumour growth paralleled with a decrease in tumour choline, as detected by non-invasive in vivo proton nuclear magnetic resonance spectroscopy. This effect was attributed to inhibition of phosphocholine de novo synthesis following decreased choline kinase α protein and messenger RNA expression that correlated with the AZD3965-induced build-up in intracellular lactate. These changes were concomitant with increased tumour immune cell infiltration involving dendritic and natural killer cells. CONCLUSIONS: Our data provide new insights into the metabolic and cellular changes that occur in the tumour microenvironment following MCT1 blockade, which may contribute to the anti-tumour activity of AZD3965 and could have potential as pharmacodynamic biomarkers of MCT1 inhibition.


Assuntos
Metabolismo dos Lipídeos/efeitos dos fármacos , Transportadores de Ácidos Monocarboxílicos/antagonistas & inibidores , Transportadores de Ácidos Monocarboxílicos/uso terapêutico , Pirimidinonas/uso terapêutico , Tiofenos/uso terapêutico , Animais , Técnicas de Cultura de Células , Linhagem Celular , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Transportadores de Ácidos Monocarboxílicos/farmacologia , Pirimidinonas/farmacologia , Tiofenos/farmacologia
5.
Magn Reson Med ; 82(2): 527-550, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30919510

RESUMO

Proton MRS (1 H MRS) provides noninvasive, quantitative metabolite profiles of tissue and has been shown to aid the clinical management of several brain diseases. Although most modern clinical MR scanners support MRS capabilities, routine use is largely restricted to specialized centers with good access to MR research support. Widespread adoption has been slow for several reasons, and technical challenges toward obtaining reliable good-quality results have been identified as a contributing factor. Considerable progress has been made by the research community to address many of these challenges, and in this paper a consensus is presented on deficiencies in widely available MRS methodology and validated improvements that are currently in routine use at several clinical research institutions. In particular, the localization error for the PRESS localization sequence was found to be unacceptably high at 3 T, and use of the semi-adiabatic localization by adiabatic selective refocusing sequence is a recommended solution. Incorporation of simulated metabolite basis sets into analysis routines is recommended for reliably capturing the full spectral detail available from short TE acquisitions. In addition, the importance of achieving a highly homogenous static magnetic field (B0 ) in the acquisition region is emphasized, and the limitations of current methods and hardware are discussed. Most recommendations require only software improvements, greatly enhancing the capabilities of clinical MRS on existing hardware. Implementation of these recommendations should strengthen current clinical applications and advance progress toward developing and validating new MRS biomarkers for clinical use.


Assuntos
Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Encéfalo/metabolismo , Consenso , Humanos , Prótons
6.
Pediatr Hematol Oncol ; 36(2): 103-112, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30978130

RESUMO

Objectives: Diffusion-weighted magnetic resonance imaging (DW-MRI) offers potential to monitor response and predict survival in high-grade gliomas (HGG) and diffuse intrinsic pontine gliomas (DIPG). We hypothesized that post-radiotherapy DW-MRI may provide prognostic imaging biomarkers in children and young adults with these tumors. Methods: Patients aged ≤21 years diagnosed between 2005 and 2012 were eligible. The tumor median apparent diffusion coefficient (ADC) and its 5th percentile (C5-ADC) were determined at the first post-radiotherapy scan and at the time of radiological progression. DW-MRI parameters were correlated with survival endpoints, temozolomide use and pseudoprogression, when it occurred. Results: Out of 40 patients (20 HGG, 20 DIPG), 23 had evaluable DW-MRI post-radiotherapy and 25 at radiological progression. There were 6 episodes of pseudoprogression. Hazard ratios (95%CI) for progression-free survival were 0.998 (0.993-1.003) for median ADC and 1.003 (0.996-1.010) for C5-ADC. Hazard ratios (95%CI) for overall survival were 1.0009 (0.996-1.006) for median ADC and 0.998 (0.992-1.004) for C5-ADC. Post-radiotherapy median and C5-ADC values were not significantly different between patients treated with radiotherapy alone versus radiotherapy/temozolomide. The median and C5-ADC values were not significantly different at the time of pseudoprogression compared to those at tumor progression. Conclusions: Post-radiotherapy median ADC and C5-ADC were not prognostic, nor able to differentiate radiosensitization with temozolomide or occurrence of pseudoprogression in this cohort of HGG and DIPG patients. Further exploration of alternative DW parameters, study timepoints or data modeling may contribute to the development of prognostic/predictive imaging biomarkers for children and young adults with HGG or DIPG.


Assuntos
Neoplasias Encefálicas/radioterapia , Imagem de Difusão por Ressonância Magnética , Glioma/radioterapia , Substância Branca/patologia , Adolescente , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias do Tronco Encefálico/tratamento farmacológico , Neoplasias do Tronco Encefálico/mortalidade , Neoplasias do Tronco Encefálico/patologia , Neoplasias do Tronco Encefálico/radioterapia , Criança , Pré-Escolar , Terapia Combinada , Difusão , Progressão da Doença , Feminino , Glioma/tratamento farmacológico , Glioma/mortalidade , Glioma/patologia , Humanos , Masculino , Prognóstico , Modelos de Riscos Proporcionais , Temozolomida/uso terapêutico , Adulto Jovem
7.
Am J Epidemiol ; 187(6): 1259-1268, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29140420

RESUMO

Mammographic percent density, the proportion of fibroglandular tissue in the breast, is a strong risk factor for breast cancer, but its determinants in young women are unknown. We examined associations of magnetic resonance imaging (MRI) breast-tissue composition at age 21 years with prospectively collected measurements of body size and composition from birth to early adulthood and markers of puberty (all standardized) in a sample of 500 nulliparous women from a prebirth cohort of children born in Avon, United Kingdom, in 1991-1992 and followed up to 2011-2014. Linear models were fitted to estimate relative change in MRI percent water, which is equivalent to mammographic percent density, associated with a 1-standard-deviation increase in the exposure of interest. In mutually adjusted analyses, MRI percent water was positively associated with birth weight (relative change (RC) = 1.03, 95% confidence interval (CI): 1.00, 1.06) and pubertal height growth (RC = 1.07, 95% CI: 1.02, 1.13) but inversely associated with pubertal weight growth (RC = 0.86, 95% CI: 0.84, 0.89) and changes in dual-energy x-ray absorptiometry percent body fat mass (e.g., for change between ages 11 years and 13.5 years, RC = 0.96, 95% CI: 0.93, 0.99). Ages at thelarche and menarche were positively associated with MRI percent water, but these associations did not persist upon adjustment for height and weight growth. These findings support the hypothesis that growth trajectories influence breast-tissue composition in young women, whereas puberty plays no independent role.


Assuntos
Composição Corporal , Mama/crescimento & desenvolvimento , Maturidade Sexual , Adolescente , Mama/diagnóstico por imagem , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Estudos Prospectivos , Puberdade , Adulto Jovem
8.
Br J Cancer ; 119(9): 1118-1128, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30377337

RESUMO

BACKGROUND: AKT is commonly overexpressed in tumours and plays an important role in the metabolic reprogramming of cancer. We have used magnetic resonance spectroscopy (MRS) to assess whether inhibition of AKT signalling would result in metabolic changes that could potentially be used as biomarkers to monitor response to AKT inhibition. METHODS: Cellular and metabolic effects of the allosteric AKT inhibitor MK-2206 were investigated in HT29 colon and PC3 prostate cancer cells and xenografts using flow cytometry, immunoblotting, immunohistology and MRS. RESULTS: In vitro treatment with MK-2206 inhibited AKT signalling and resulted in time-dependent alterations in glucose, glutamine and phospholipid metabolism. In vivo, MK-2206 resulted in inhibition of AKT signalling and tumour growth compared with vehicle-treated controls. In vivo MRS analysis of HT29 subcutaneous xenografts showed similar metabolic changes to those seen in vitro including decreases in the tCho/water ratio, tumour bioenergetic metabolites and changes in glutamine and glutathione metabolism. Similar phosphocholine changes compared to in vitro were confirmed in the clinically relevant orthotopic PC3 model. CONCLUSION: This MRS study suggests that choline metabolites detected in response to AKT inhibition are time and microenvironment-dependent, and may have potential as non-invasive biomarkers for monitoring response to AKT inhibitors in selected cancer types.


Assuntos
Antineoplásicos/farmacologia , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Inibidores Enzimáticos/farmacologia , Compostos Heterocíclicos com 3 Anéis/farmacologia , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , Xenoenxertos , Humanos , Espectroscopia de Ressonância Magnética/métodos , Masculino
9.
Eur J Nucl Med Mol Imaging ; 45(5): 759-767, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29164301

RESUMO

OBJECTIVE: To assess the optimal timing and predictive value of early intra-treatment changes in multimodality functional and molecular imaging (FMI) parameters as biomarkers for clinical remission in patients receiving chemoradiation for head and neck squamous cell carcinoma (HNSCC). METHODS: Thirty-five patients with stage III-IVb (AJCC 7th edition) HNSCC prospectively underwent 18F-FDG-PET/CT, and diffusion-weighted (DW), dynamic contrast-enhanced (DCE) and susceptibility-weighted MRI at baseline, week 1 and week 2 of chemoradiation. Patients with evidence of persistent or recurrent disease during follow-up were classed as non-responders. Changes in FMI parameters at week 1 and week 2 were compared between responders and non-responders with the Mann-Whitney U test. The significance threshold was set at a p value of <0.05. RESULTS: There were 27 responders and 8 non-responders. Responders showed a greater reduction in PET-derived tumor total lesion glycolysis (TLG40%; p = 0.007) and maximum standardized uptake value (SUVmax; p = 0.034) after week 1 than non-responders but these differences were absent by week 2. In contrast, it was not until week 2 that MRI-derived parameters were able to discriminate between the two groups: larger fractional increases in primary tumor apparent diffusion coefficient (ADC; p < 0.001), volume transfer constant (Ktrans; p = 0.012) and interstitial space volume fraction (Ve; p = 0.047) were observed in responders versus non-responders. ADC was the most powerful predictor (∆ >17%, AUC 0.937). CONCLUSION: Early intra-treatment changes in FDG-PET, DW and DCE MRI-derived parameters are predictive of ultimate response to chemoradiation in HNSCC. However, the optimal timing for assessment with FDG-PET parameters (week 1) differed from MRI parameters (week 2). This highlighted the importance of scanning time points for the design of FMI risk-stratified interventional studies.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Quimiorradioterapia , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Imagem Multimodal , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Carcinoma de Células Escamosas/terapia , Imagem de Difusão por Ressonância Magnética , Feminino , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons
10.
Eur Radiol ; 28(4): 1642-1653, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29038934

RESUMO

OBJECTIVES: To determine the ability of multi-parametric, endogenous contrast MRI to detect and quantify fibrosis in a chemically-induced rat model of mammary carcinoma. METHODS: Female Sprague-Dawley rats (n=18) were administered with N-methyl-N-nitrosourea; resulting mammary carcinomas underwent nine-b-value diffusion-weighted (DWI), ultrashort-echo (UTE) and magnetisation transfer (MT) magnetic resonance imaging (MRI) on a clinical 1.5T platform, and associated quantitative MR parameters were calculated. Excised tumours were histologically assessed for degree of necrosis, collagen, hypoxia and microvessel density. Significance level adjusted for multiple comparisons was p=0.0125. RESULTS: Significant correlations were found between MT parameters and degree of picrosirius red staining (r > 0.85, p < 0.0002 for ka and δ, r < -0.75, p < 0.001 for T1 and T1s, Pearson), indicating that MT is sensitive to collagen content in mammary carcinoma. Picrosirius red also correlated with the DWI parameter fD* (r=0.801, p=0.0004) and conventional gradient-echo T2* (r=-0.660, p=0.0055). Percentage necrosis correlated moderately with ultrashort/conventional-echo signal ratio (r=0.620, p=0.0105). Pimonidazole adduct (hypoxia) and CD31 (microvessel density) staining did not correlate with any MR parameter assessed. CONCLUSIONS: Magnetisation transfer MRI successfully detects collagen content in mammary carcinoma, supporting inclusion of MT imaging to identify fibrosis, a prognostic marker, in clinical breast MRI examinations. KEY POINTS: • Magnetisation transfer imaging is sensitive to collagen content in mammary carcinoma. • Magnetisation transfer imaging to detect fibrosis in mammary carcinoma fibrosis is feasible. • IVIM diffusion does not correlate with microvessel density in preclinical mammary carcinoma.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/patologia , Animais , Meios de Contraste , Feminino , Fibrose/diagnóstico por imagem , Humanos , Necrose/diagnóstico por imagem , Nitroimidazóis , Molécula-1 de Adesão Celular Endotelial a Plaquetas , Ratos Sprague-Dawley
11.
Pediatr Radiol ; 48(11): 1630-1641, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30062569

RESUMO

BACKGROUND: A tool for diagnosing childhood cerebellar tumours using magnetic resonance (MR) spectroscopy peak height measurement has been developed based on retrospective analysis of single-centre data. OBJECTIVE: To determine the diagnostic accuracy of the peak height measurement tool in a multicentre prospective study, and optimise it by adding new prospective data to the original dataset. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) and single-voxel MR spectroscopy were performed on children with cerebellar tumours at three centres. Spectra were processed using standard scanner software and peak heights for N-acetyl aspartate, creatine, total choline and myo-inositol were measured. The original diagnostic tool was used to classify 26 new tumours as pilocytic astrocytoma, medulloblastoma or ependymoma. These spectra were subsequently combined with the original dataset to develop an optimised scheme from 53 tumours in total. RESULTS: Of the pilocytic astrocytomas, medulloblastomas and ependymomas, 65.4% were correctly assigned using the original tool. An optimized scheme was produced from the combined dataset correctly assigning 90.6%. Rare tumour types showed distinctive MR spectroscopy features. CONCLUSION: The original diagnostic tool gave modest accuracy when tested prospectively on multicentre data. Increasing the dataset provided a diagnostic tool based on MR spectroscopy peak height measurement with high levels of accuracy for multicentre data.


Assuntos
Neoplasias Cerebelares/diagnóstico por imagem , Espectroscopia de Ressonância Magnética/métodos , Biomarcadores Tumorais/metabolismo , Neoplasias Cerebelares/metabolismo , Criança , Diagnóstico Diferencial , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Estudos Prospectivos
12.
Br J Cancer ; 116(1): 28-35, 2017 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-27884018

RESUMO

BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) undergoing radical chemo-radiation (CRT) frequently receive transfusion with packed red cells (PRCT) during radiotherapy on the basis that PRCT increases tumour oxygenation and overcomes hypoxia-induced radio-resistance. This is likely to be a significant oversimplification given the fact that tumour hypoxia is the result of several intrinsic and extrinsic factors, including many that are not directly related to serum haemoglobin (Hb). Therefore, we have studied the effect of PRCT on tumour oxygenation in a prospective cohort of patients who developed low Hb during radical CRT for HNSCC. METHODS: This was a prospective study of 20 patients with HNSCC receiving radical CRT undergoing PRCT for Hb<11.5 g dl-1. Patients underwent pretransfusion and posttransfusion intrinsic susceptibility-weighted (SWI) MRI and dynamic contrast-enhanced (DCE) MRI. Blood samples were obtained at the time of MRI scanning and two further time points for measuring Hb and a panel of serum cytokine markers of tumour hypoxia. 3D T2* and Ktrans maps were calculated from the MRI data for primary tumours and cervical lymph node metastases. RESULTS: PRCT produced no change (11 patients) or reduced (1 patient) T2* (tumour oxygenation) in 12 of the 16 (75%) evaluable primary tumours. Three of the four patients with improved tumour oxygenation progressed or had partial response following treatment completion. There were variable changes in Ktrans (tumour perfusion or vessel permeability) following PRCT that were of small magnitude for most tumours. Pre- and Post-PRCT levels of measured cytokines were not significantly different. CONCLUSIONS: This study suggests that PRCT during radical CRT for HNSCC does not improve tumour oxygenation. Therefore, oncologists should consider changing practice according to NICE and American Association of Blood Banks guidelines on PRCT for anaemia.


Assuntos
Transfusão de Sangue , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Neoplasias de Cabeça e Pescoço/terapia , Hipóxia Tumoral , Idoso , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estudos Longitudinais , Metástase Linfática , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço , Hipóxia Tumoral/efeitos dos fármacos
13.
Radiology ; 284(1): 88-99, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28301311

RESUMO

Purpose To assess the repeatability of apparent diffusion coefficient (ADC) estimates in extracranial soft-tissue diffusion-weighted magnetic resonance imaging across a wide range of imaging protocols and patient populations. Materials and Methods Nine prospective patient studies and one prospective volunteer study, performed between 2006 and 2016 with research ethics committee approval and written informed consent from each subject, were included in this single-institution study. A total of 141 tumors and healthy organs were imaged twice (interval between repeated examinations, 45 minutes to 10 days, depending the on study) to assess the repeatability of median and mean ADC estimates. The Levene test was used to determine whether ADC repeatability differed between studies. The Pearson linear correlation coefficient was used to assess correlation between coefficient of variation (CoV) and the year the study started, study size, and volumes of tumors and healthy organs. The repeatability of ADC estimates from small, medium, and large tumors and healthy organs was assessed irrespective of study, and the Levene test was used to determine whether ADC repeatability differed between these groups. Results CoV aggregated across all studies was 4.1% (range for each study, 1.7%-6.5%). No correlation was observed between CoV and the year the study started or study size. CoV was weakly correlated with volume (r = -0.5, P = .1). Repeatability was significantly different between small, medium, and large tumors (P < .05), with the lowest CoV (2.6%) for large tumors. There was a significant difference in repeatability between studies-a difference that did not persist after the study with the largest tumors was excluded. Conclusion ADC is a robust imaging metric with excellent repeatability in extracranial soft tissues across a wide range of tumor sites, sizes, patient populations, and imaging protocol variations. Online supplemental material is available for this article.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias de Tecidos Moles/diagnóstico por imagem , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes
14.
Radiology ; 283(1): 168-177, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27875103

RESUMO

Purpose To determine the usefulness of whole-body diffusion-weighted imaging (DWI) to assess the response of bone metastases to treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods A phase II prospective clinical trial of the poly-(adenosine diphosphate-ribose) polymerase inhibitor olaparib in mCRPC included a prospective magnetic resonance (MR) imaging substudy; the study was approved by the institutional research board, and written informed consent was obtained. Whole-body DWI was performed at baseline and after 12 weeks of olaparib administration by using 1.5-T MR imaging. Areas of abnormal signal intensity on DWI images in keeping with bone metastases were delineated to derive total diffusion volume (tDV); five target lesions were also evaluated. Associations of changes in volume of bone metastases and median apparent diffusion coefficient (ADC) with response to treatment were assessed by using the Mann-Whitney test and logistic regression; correlation with prostate-specific antigen level and circulating tumor cell count were assessed by using Spearman correlation (r). Results Twenty-one patients were included. All six responders to olaparib showed a decrease in tDV, while no decrease was observed in all nonresponders; this difference between responders and nonresponders was significant (P = .001). Increases in median ADC were associated with increased odds of response (odds ratio, 1.08; 95% confidence interval [CI]: 1.00, 1.15; P = .04). A positive association was detected between changes in tDV and best percentage change in prostate-specific antigen level and circulating tumor cell count (r = 0.63 [95% CI: 0.27, 0.83] and r = 0.77 [95% CI: 0.51, 0.90], respectively). When assessing five target lesions, decreases in volume were associated with response (odds ratio for volume increase, 0.89; 95% CI: 0.80, 0.99; P = .037). Conclusion This pilot study showed that decreases in volume and increases in median ADC of bone metastases assessed with whole-body DWI can potentially be used as indicators of response to olaparib in mCRPC. Online supplemental material is available for this article.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias da Próstata/patologia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais , Neoplasias Ósseas/tratamento farmacológico , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Ftalazinas/uso terapêutico , Projetos Piloto , Piperazinas/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento , Imagem Corporal Total
15.
Eur Radiol ; 27(1): 345-353, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27003140

RESUMO

OBJECTIVES: To examine repeatability of parameters derived from non-Gaussian diffusion models in data acquired in children with solid tumours. METHODS: Paediatric patients (<16 years, n = 17) were scanned twice, 24 h apart, using DWI (6 b-values, 0-1000 mm-2 s) at 1.5 T in a prospective study. Tumour ROIs were drawn (3 slices) and all data fitted using IVIM, stretched exponential, and kurtosis models; percentage coefficients of variation (CV) calculated for each parameter at all ROI histogram centiles, including the medians. RESULTS: The values for ADC, D, DDCα, α, and DDCK gave CV < 10 % down to the 5th centile, with sharp CV increases below 5th and above 95th centile. K, f, and D* showed increased CV (>30 %) over the histogram. ADC, D, DDCα, and DDCK were strongly correlated (ρ > 0.9), DDCα and α were not correlated (ρ = 0.083). CONCLUSION: Perfusion- and kurtosis-related parameters displayed larger, more variable CV across the histogram, indicating observed clinical changes outside of D/DDC in these models should be interpreted with caution. Centiles below 5th for all parameters show high CV and are unreliable as diffusion metrics. The stretched exponential model behaved well for both DDCα and α, making it a strong candidate for modelling multiple-b-value diffusion imaging data. KEY POINTS: • ADC has good repeatability as low 5th centile of the histogram distribution. • High CV was observed for all parameters at extremes of histogram. • Parameters from the stretched exponential model showed low coefficients of variation. • The median ADC, D, DDC α , and DDC K are highly correlated and repeatable. • Perfusion/kurtosis parameters showed high CV variations across their histogram distributions.


Assuntos
Imagem de Difusão por Ressonância Magnética/estatística & dados numéricos , Modelos Teóricos , Neoplasias/diagnóstico por imagem , Adolescente , Criança , Estudos de Coortes , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes
16.
Pediatr Blood Cancer ; 64(2): 279-283, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27615273

RESUMO

Diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) have been used as imaging biomarkers in adults with high-grade gliomas (HGGs). We incorporated free-breathing DW-MRI and DCE-MRI, at a single time point, in the routine follow-up of five children (median age 9 years, range 8-15) with histologically confirmed HGG within a prospective imaging study. It was feasible to incorporate DW-MRI and DCE-MRI in routine assessments of children with HGG. DW and DCE parameters were repeatable in paediatric HGG. Higher median ADC100-1000 significantly correlated with longer survival in our sample.


Assuntos
Neoplasias Encefálicas/diagnóstico , Meios de Contraste , Imagem de Difusão por Ressonância Magnética/métodos , Glioma/diagnóstico , Processamento de Imagem Assistida por Computador/métodos , Adolescente , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Criança , Estudos de Viabilidade , Feminino , Seguimentos , Glioma/diagnóstico por imagem , Humanos , Masculino , Gradação de Tumores , Prognóstico , Adulto Jovem
17.
J Appl Clin Med Phys ; 18(2): 154-162, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28300372

RESUMO

An Active Breathing Coordinator (ABC) can be employed to induce breath-holds during CT imaging and radiotherapy of lung, breast and liver cancer, and recently during lung cancer MRI. The apparatus measures and controls respiratory volume, hence subject lung volume reproducibility is its principal measure of effectiveness. To assess ABC control quality, the intra-session reproducibility of ABC-induced lung volumes was evaluated and compared with that reached by applying the clinical standard of operator-guided self-sustained breath-holds on healthy volunteers during MRI. Inter-session reproducibility was investigated by repeating ABC-controlled breath-holds on a second visit. Additionally, lung volume agreement with ABC devices used with different imaging modalities in the same institution (MR, CT), or for a breast trial treatment, was assessed. Lung volumes were derived from three-dimensional (3D) T1-weighted MRI datasets by three observers employing semiautomatic lung delineation on a radiotherapy treatment planning system. Inter-observer variability was less than 6% of the delineated lung volumes. Lung volume agreement between the different conditions over all subjects was investigated using descriptive statistics. The ABC equipment dedicated for MR application exhibited good intra-session and inter-session lung volume reproducibility (1.8% and 3% lung volume variability on average, respectively). MR-assessed lung volumes were similar using different ABC equipment dedicated to MR, CT, or breast radiotherapy. Overall, lung volumes controlled by the same or different ABC devices agreed better than with self-controlled breath-holds, as suggested by the average ABC variation of 1.8% of the measured lung volumes (99 mL), compared to the 4.1% (226 mL) variability observed on average with self-sustained breath-holding.


Assuntos
Neoplasias da Mama/patologia , Suspensão da Respiração , Pulmão/efeitos da radiação , Imageamento por Ressonância Magnética/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Adulto , Neoplasias da Mama/radioterapia , Feminino , Voluntários Saudáveis , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/instrumentação , Masculino , Pessoa de Meia-Idade , Movimento , Posicionamento do Paciente , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Reprodutibilidade dos Testes , Respiração , Técnicas de Imagem de Sincronização Respiratória/métodos
18.
Breast Cancer Res ; 18(1): 102, 2016 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-27729066

RESUMO

BACKGROUND: Breast density, the amount of fibroglandular tissue in the adult breast for a women's age and body mass index, is a strong biomarker of susceptibility to breast cancer, which may, like breast cancer risk itself, be influenced by events early in life. In the present study, we investigated the association between pre-natal exposures and breast tissue composition. METHODS: A sample of 500 young, nulliparous women (aged approximately 21 years) from a U.K. pre-birth cohort underwent a magnetic resonance imaging examination of their breasts to estimate percent water, a measure of the relative amount of fibroglandular tissue equivalent to mammographic percent density. Information on pre-natal exposures was collected throughout the mothers' pregnancy and shortly after delivery. Regression models were used to investigate associations between percent water and pre-natal exposures. Mediation analysis, and a systematic review and meta-analysis of the published literature, were also conducted. RESULTS: Adjusted percent water in young women was positively associated with maternal height (p for linear trend [p t] = 0.005), maternal mammographic density in middle age (p t = 0.018) and the participant's birth size (p t < 0.001 for birthweight). A 1-SD increment in weight (473 g), length (2.3 cm), head circumference (1.2 cm) and Ponderal Index (4.1 g/cm3) at birth were associated with 3 % (95 % CI 2-5 %), 2 % (95 % CI 0-3 %), 3 % (95 % CI 1-4 %) and 1 % (95 % CI 0-3 %), respectively, increases in mean adjusted percent water. The effect of maternal height on the participants' percent water was partly mediated through birth size, but there was little evidence that the effect of birthweight was primarily mediated via adult body size. The meta-analysis supported the study findings, with breast density being positively associated with birth size. CONCLUSIONS: These findings provide strong evidence of pre-natal influences on breast tissue composition. The positive association between birth size and relative amount of fibroglandular tissue indicates that breast density and breast cancer risk may share a common pre-natal origin.


Assuntos
Glândulas Mamárias Humanas/diagnóstico por imagem , Exposição Materna , Efeitos Tardios da Exposição Pré-Natal , Adulto , Densidade da Mama , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Glândulas Mamárias Humanas/patologia , Exposição Materna/efeitos adversos , Vigilância da População , Gravidez , Fatores de Risco , Reino Unido/epidemiologia , Adulto Jovem
19.
Br J Cancer ; 114(6): 631-7, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26908327

RESUMO

BACKGROUND: We investigated the additional contribution of mammography to screening accuracy in BRCA1/2 mutation carriers screened with MRI at different ages using individual patient data from six high-risk screening trials. METHODS: Sensitivity and specificity of MRI, mammography and the combination of these tests were compared stratified for BRCA mutation and age using generalised linear mixed models with random effect for studies. Number of screens needed (NSN) for additional mammography-only detected cancer was estimated. RESULTS: In BRCA1/2 mutation carriers of all ages (BRCA1 = 1,219 and BRCA2 = 732), adding mammography to MRI did not significantly increase screening sensitivity (increased by 3.9% in BRCA1 and 12.6% in BRCA2 mutation carriers, P > 0.05). However, in women with BRCA2 mutation younger than 40 years, one-third of breast cancers were detected by mammography only. Number of screens needed for mammography to detect one breast cancer not detected by MRI was much higher for BRCA1 compared with BRCA2 mutation carriers at initial and repeat screening. CONCLUSIONS: Additional screening sensitivity from mammography above that from MRI is limited in BRCA1 mutation carriers, whereas mammography contributes to screening sensitivity in BRCA2 mutation carriers, especially those ⩽ 40 years. The evidence from our work highlights that a differential screening schedule by BRCA status is worth considering.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Genes BRCA1 , Genes BRCA2 , Mutação , Adulto , Fatores Etários , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Mamografia/métodos , Pessoa de Meia-Idade
20.
Radiology ; 280(1): 151-60, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26807894

RESUMO

Purpose To determine the correlation between the volume of bone metastasis as assessed with diffusion-weighted (DW) imaging and established prognostic factors in metastatic castration-resistant prostate cancer (mCRPC) and the association with overall survival (OS). Materials and Methods This retrospective study was approved by the institutional review board; informed consent was obtained from all patients. The authors analyzed whole-body DW images obtained between June 2010 and February 2013 in 53 patients with mCRPC at the time of starting a new line of anticancer therapy. Bone metastases were identified and delineated on whole-body DW images in 43 eligible patients. Total tumor diffusion volume (tDV) was correlated with the bone scan index (BSI) and other prognostic factors by using the Pearson correlation coefficient (r). Survival analysis was performed with Kaplan-Meier analysis and Cox regression. Results The median tDV was 503.1 mL (range, 5.6-2242 mL), and the median OS was 12.9 months (95% confidence interval [CI]: 8.7, 16.1 months). There was a significant correlation between tDV and established prognostic factors, including hemoglobin level (r = -0.521, P < .001), prostate-specific antigen level (r = 0.556, P < .001), lactate dehydrogenase level (r = 0.534, P < .001), alkaline phosphatase level (r = 0.572, P < .001), circulating tumor cell count (r = 0.613, P = .004), and BSI (r = 0.565, P = .001). A higher tDV also showed a significant association with poorer OS (hazard ratio, 1.74; 95% CI: 1.02, 2.96; P = .035). Conclusion Metastatic bone disease from mCRPC can be evaluated and quantified with whole-body DW imaging. Whole-body DW imaging-generated tDV showed correlation with established prognostic biomarkers and is associated with OS in mCRPC. (©) RSNA, 2016 Online supplemental material is available for this article.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias de Próstata Resistentes à Castração/patologia , Imagem Corporal Total/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/patologia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Estudos Retrospectivos , Carga Tumoral
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