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2.
Nat Commun ; 13(1): 466, 2022 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-35075123

RESUMO

Hyperpolarised magnetic resonance imaging (HP 13C-MRI) is an emerging clinical technique to detect [1-13C]lactate production in prostate cancer (PCa) following intravenous injection of hyperpolarised [1-13C]pyruvate. Here we differentiate clinically significant PCa from indolent disease in a low/intermediate-risk population by correlating [1-13C]lactate labelling on MRI with the percentage of Gleason pattern 4 (%GP4) disease. Using immunohistochemistry and spatial transcriptomics, we show that HP 13C-MRI predominantly measures metabolism in the epithelial compartment of the tumour, rather than the stroma. MRI-derived tumour [1-13C]lactate labelling correlated with epithelial mRNA expression of the enzyme lactate dehydrogenase (LDHA and LDHB combined), and the ratio of lactate transporter expression between the epithelial and stromal compartments (epithelium-to-stroma MCT4). We observe similar changes in MCT4, LDHA, and LDHB between tumours with primary Gleason patterns 3 and 4 in an independent TCGA cohort. Therefore, HP 13C-MRI can metabolically phenotype clinically significant disease based on underlying metabolic differences in the epithelial and stromal tumour compartments.


Assuntos
Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Células Epiteliais/metabolismo , Glicólise , Humanos , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Estudos Prospectivos , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/genética , Ácido Pirúvico/metabolismo , Células Estromais/metabolismo
3.
Cancer Res ; 81(23): 6004-6017, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34625424

RESUMO

Hyperpolarized 13C-MRI is an emerging tool for probing tissue metabolism by measuring 13C-label exchange between intravenously injected hyperpolarized [1-13C]pyruvate and endogenous tissue lactate. Here, we demonstrate that hyperpolarized 13C-MRI can be used to detect early response to neoadjuvant therapy in breast cancer. Seven patients underwent multiparametric 1H-MRI and hyperpolarized 13C-MRI before and 7-11 days after commencing treatment. An increase in the lactate-to-pyruvate ratio of approximately 20% identified three patients who, following 5-6 cycles of treatment, showed pathological complete response. This ratio correlated with gene expression of the pyruvate transporter MCT1 and lactate dehydrogenase A (LDHA), the enzyme catalyzing label exchange between pyruvate and lactate. Analysis of approximately 2,000 breast tumors showed that overexpression of LDHA and the hypoxia marker CAIX was associated with reduced relapse-free and overall survival. Hyperpolarized 13C-MRI represents a promising method for monitoring very early treatment response in breast cancer and has demonstrated prognostic potential. SIGNIFICANCE: Hyperpolarized carbon-13 MRI allows response assessment in patients with breast cancer after 7-11 days of neoadjuvant chemotherapy and outperformed state-of-the-art and research quantitative proton MRI techniques.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Isótopos de Carbono/análise , Imageamento por Ressonância Magnética/métodos , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Feminino , Seguimentos , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Prognóstico , Taxa de Sobrevida
4.
Magn Reson Med ; 86(3): 1734-1745, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33934383

RESUMO

PURPOSE: An unmet need in carbon-13 (13 C)-MRI is a transmit system that provides uniform excitation across a large FOV and can accommodate patients of wide-ranging body habitus. Due to the small difference between the resonant frequencies, sodium-23 (23 Na) coil developments can inform 13 C coil design while being simpler to assess due to the higher naturally abundant 23 Na signal. Here we present a removable 23 Na birdcage, which also allows operation as a 13 C abdominal coil. METHODS: We demonstrate a quadrature-driven 4-rung 23 Na birdcage coil of 50 cm in length for both 23 Na and 13 C abdominal imaging. The coil transmit efficiencies and B1+ maps were compared to a linearly driven 13 C Helmholtz-based (clamshell) coil. SNR was investigated with 23 Na and 13 C data using an 8-channel 13 C receive array within the 23 Na birdcage. RESULTS: The 23 Na birdcage longitudinal FOV was > 40 cm, whereas the 13 C clamshell was < 32 cm. The transmit efficiency of the birdcage at the 23 Na frequency was 0.65 µT/sqrt(W), similar to the clamshell for 13 C. However, the coefficient of variation of 23 Na- B1+ was 16%, nearly half that with the 13 C clamshell. The 8-channel 13 C receive array combined with the 23 Na birdcage coil generated a greater than twofold increase in 23 Na-SNR from the central abdomen compared with the birdcage alone. DISCUSSION: This 23 Na birdcage coil has a larger FOV and improved B1+ uniformity when compared to the widely used clamshell coil design while also providing similar transmit efficiency. The coil has the potential to be used for both 23 Na and 13 C imaging.


Assuntos
Imageamento por Ressonância Magnética , Sódio , Abdome , Desenho de Equipamento , Humanos , Imagens de Fantasmas
5.
R Soc Open Sci ; 4(2): 160731, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28386427

RESUMO

The high-fidelity reconstruction of compressed and low-resolution magnetic resonance (MR) data is essential for simultaneously improving patient care, accuracy in diagnosis and quality in clinical research. Sponsored by the Royal Society through the Newton Mobility Grant Scheme, we held a half-day workshop on reconstruction schemes for MR data on 17 August 2016 to discuss new ideas from related research fields that could be useful to overcome the shortcomings of the conventional reconstruction methods that have been evaluated to date. Participants were 21 university students, computer scientists, image analysts, engineers and physicists from institutions from six different countries. The discussion evolved around exploring new avenues to achieve high resolution, high quality and fast acquisition of MR imaging. In this article, we summarize the topics covered throughout the workshop and make recommendations for ongoing and future works.

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