Fat Fraction MRI for Longitudinal Assessment of Bone Marrow Heterogeneity in a Mouse Model of Myelofibrosis.

IF 2.2 4区医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Tomography Pub Date : 2025-07-28 DOI:10.3390/tomography11080082

Lauren Brenner, Tanner H Robison, Timothy D Johnson, Kristen Pettit, Moshe Talpaz, Thomas L Chenevert, Brian D Ross, Gary D Luker

{"title":"Fat Fraction MRI for Longitudinal Assessment of Bone Marrow Heterogeneity in a Mouse Model of Myelofibrosis.","authors":"Lauren Brenner, Tanner H Robison, Timothy D Johnson, Kristen Pettit, Moshe Talpaz, Thomas L Chenevert, Brian D Ross, Gary D Luker","doi":"10.3390/tomography11080082","DOIUrl":null,"url":null,"abstract":"Background/objectives: Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by the replacement of healthy bone marrow (BM) with malignant and fibrotic tissue. In a healthy state, bone marrow is composed of approximately 60-70% fat cells, which are replaced as disease progresses. Proton density fat fraction (PDFF), a non-invasive and quantitative MRI metric, enables analysis of BM architecture by measuring the percentage of fat versus cells in the environment. Our objective is to investigate variance in quantitative PDFF-MRI values over time as a marker of disease progression and response to treatment.Methods: We analyzed existing data from three cohorts of mice: two groups with MF that failed to respond to therapy with approved drugs for MF (ruxolitinib, fedratinib), investigational compounds (navitoclax, balixafortide), or vehicle and monitored over time by MRI; the third group consisted of healthy controls imaged at a single time point. Using in-house MATLAB programs, we performed a voxel-wise analysis of PDFF values in lower extremity bone marrow, specifically comparing the variance of each voxel within and among mice.Results: Our findings revealed a significant difference in PDFF values between healthy and diseased BM. With progressive disease non-responsive to therapy, the expansion of hematopoietic cells in BM nearly completely replaced normal fat, as determined by a markedly reduced PDFF and notable reduction in the variance in PDFF values in bone marrow over time.Conclusions: This study validated our hypothesis that the variance in PDFF in BM decreases with disease progression, indicating pathologic expansion of hematopoietic cells. We can conclude that disease progression can be tracked by a decrease in PDFF values. Analyzing variance in PDFF may improve the assessment of disease progression in pre-clinical models and ultimately patients with MF.","PeriodicalId":51330,"journal":{"name":"Tomography","volume":"11 8","pages":""},"PeriodicalIF":2.2000,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12390422/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tomography","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/tomography11080082","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}

引用次数: 0

Abstract

Background/objectives: Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by the replacement of healthy bone marrow (BM) with malignant and fibrotic tissue. In a healthy state, bone marrow is composed of approximately 60-70% fat cells, which are replaced as disease progresses. Proton density fat fraction (PDFF), a non-invasive and quantitative MRI metric, enables analysis of BM architecture by measuring the percentage of fat versus cells in the environment. Our objective is to investigate variance in quantitative PDFF-MRI values over time as a marker of disease progression and response to treatment.

Methods: We analyzed existing data from three cohorts of mice: two groups with MF that failed to respond to therapy with approved drugs for MF (ruxolitinib, fedratinib), investigational compounds (navitoclax, balixafortide), or vehicle and monitored over time by MRI; the third group consisted of healthy controls imaged at a single time point. Using in-house MATLAB programs, we performed a voxel-wise analysis of PDFF values in lower extremity bone marrow, specifically comparing the variance of each voxel within and among mice.

Results: Our findings revealed a significant difference in PDFF values between healthy and diseased BM. With progressive disease non-responsive to therapy, the expansion of hematopoietic cells in BM nearly completely replaced normal fat, as determined by a markedly reduced PDFF and notable reduction in the variance in PDFF values in bone marrow over time.

Conclusions: This study validated our hypothesis that the variance in PDFF in BM decreases with disease progression, indicating pathologic expansion of hematopoietic cells. We can conclude that disease progression can be tracked by a decrease in PDFF values. Analyzing variance in PDFF may improve the assessment of disease progression in pre-clinical models and ultimately patients with MF.

Abstract Image

查看原文本刊更多论文

脂肪分数MRI纵向评估骨髓纤维化小鼠模型的骨髓异质性。

背景/目的：骨髓纤维化（MF）是一种骨髓增生性肿瘤，其特征是恶性和纤维化组织取代健康骨髓（BM）。在健康状态下，骨髓由大约60-70%的脂肪细胞组成，随着疾病的进展，脂肪细胞被取代。质子密度脂肪分数（PDFF）是一种非侵入性的定量MRI指标，可以通过测量环境中脂肪与细胞的百分比来分析BM结构。我们的目的是调查定量PDFF-MRI值随时间的变化，作为疾病进展和对治疗反应的标志。方法：我们分析了来自三组小鼠的现有数据：两组MF患者对批准的MF药物（ruxolitinib, fedratinib），研究化合物（navitoclax, balixafortide）或车辆治疗无效，并通过MRI监测一段时间；第三组包括在单一时间点成像的健康对照。使用内部MATLAB程序，我们对下肢骨髓中的PDFF值进行了体素分析，特别比较了小鼠体内和小鼠之间每个体素的方差。结果：我们的研究结果显示，健康和患病BM之间的PDFF值有显著差异。随着疾病的进展，对治疗无反应，骨髓中造血细胞的扩张几乎完全取代了正常脂肪，这是由骨髓中PDFF的显著降低和PDFF值随时间变化的显著减少所确定的。结论：本研究证实了我们的假设，即BM中PDFF的方差随着疾病进展而降低，表明造血细胞的病理扩增。我们可以得出结论，疾病进展可以通过PDFF值的下降来跟踪。分析PDFF的方差可以改善临床前模型和最终MF患者的疾病进展评估。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Tomography Medicine-Radiology, Nuclear Medicine and Imaging

CiteScore

2.70

自引率

10.50%

发文量

222

期刊介绍： TomographyTM publishes basic (technical and pre-clinical) and clinical scientific articles which involve the advancement of imaging technologies. Tomography encompasses studies that use single or multiple imaging modalities including for example CT, US, PET, SPECT, MR and hyperpolarization technologies, as well as optical modalities (i.e. bioluminescence, photoacoustic, endomicroscopy, fiber optic imaging and optical computed tomography) in basic sciences, engineering, preclinical and clinical medicine. Tomography also welcomes studies involving exploration and refinement of contrast mechanisms and image-derived metrics within and across modalities toward the development of novel imaging probes for image-based feedback and intervention. The use of imaging in biology and medicine provides unparalleled opportunities to noninvasively interrogate tissues to obtain real-time dynamic and quantitative information required for diagnosis and response to interventions and to follow evolving pathological conditions. As multi-modal studies and the complexities of imaging technologies themselves are ever increasing to provide advanced information to scientists and clinicians. Tomography provides a unique publication venue allowing investigators the opportunity to more precisely communicate integrated findings related to the diverse and heterogeneous features associated with underlying anatomical, physiological, functional, metabolic and molecular genetic activities of normal and diseased tissue. Thus Tomography publishes peer-reviewed articles which involve the broad use of imaging of any tissue and disease type including both preclinical and clinical investigations. In addition, hardware/software along with chemical and molecular probe advances are welcome as they are deemed to significantly contribute towards the long-term goal of improving the overall impact of imaging on scientific and clinical discovery.