Hui Susanta K, Arentsen Luke, Sueblinvong Thanasak, Brown Keenan, Bolan Pat, Ghebre Rahel G, Downs Levi, Shanley Ryan, Hansen Karen E, Minenko Anne G, Takhashi Yutaka, Yagi Masashi, Zhang Yan, Geller Melissa, Reynolds Margaret, Lee Chung K, Blaes Anne H, Allen Sharon, Zobel Bruno Beomonte, Le Chap, Froelich Jerry, Rosen Clifford, Yee Douglas
Department of Therapeutic Radiology, University of Minnesota, MN, USA; Masonic Cancer Center, University of Minnesota, MN, USA.
Department of Therapeutic Radiology, University of Minnesota, MN, USA.
Bone. 2015 Apr;73:90-7. doi: 10.1016/j.bone.2014.12.014. Epub 2014 Dec 20.
Cancer survivors are at an increased risk for fractures, but lack of effective and economical biomarkers limits quantitative assessments of marrow fat (MF), bone mineral density (BMD) and their relation in response to cytotoxic cancer treatment. We report dual energy CT (DECT) imaging, commonly used for cancer diagnosis, treatment and surveillance, as a novel biomarker of MF and BMD.
We validated DECT in pre-clinical and phase I clinical trials and verified with water-fat MRI (WF-MRI), quantitative CT (QCT) and dual-energy X-ray absorptiometry (DXA). Basis material composition framework was validated using water and small-chain alcohols simulating different components of bone marrow. Histologic validation was achieved by measuring percent adipocyte in the cadaver vertebrae and compared with DECT and WF-MRI. For a phase I trial, sixteen patients with gynecologic malignancies (treated with oophorectomy, radiotherapy or chemotherapy) underwent DECT, QCT, WF-MRI and DXA before and 12months after treatment. BMD and MF percent and distribution were quantified in the lumbar vertebrae and the right femoral neck.
Measured precision (3mg/cm(3)) was sufficient to distinguish test solutions. Adiposity in cadaver bone histology was highly correlated with MF measured using DECT and WF-MRI (r=0.80 and 0.77, respectively). In the clinical trial, DECT showed high overall correlation (r=0.77, 95% CI: 0.69, 0.83) with WF-MRI. MF increased significantly after treatment (p<0.002). Chemotherapy and radiation caused greater increases in MF than oophorectomy (p<0.032). L4 BMD decreased 14% by DECT, 20% by QCT, but only 5% by DXA (p<0.002 for all). At baseline, we observed a statistically significant inverse association between MF and BMD which was dramatically attenuated after treatment.
Our study demonstrated that DECT, similar to WF-MRI, can accurately measure marrow adiposity. Both imaging modalities show rapid increase in MF following cancer treatment. Our results suggest that MF and BMD cannot be used interchangeably to monitor skeletal health following cancer therapy.
癌症幸存者骨折风险增加，但缺乏有效且经济的生物标志物限制了对骨髓脂肪（MF）、骨密度（BMD）及其在细胞毒性癌症治疗反应中的关系进行定量评估。我们报告了常用于癌症诊断、治疗和监测的双能CT（DECT）成像，作为MF和BMD的一种新型生物标志物。
我们在临床前和I期临床试验中验证了DECT，并用水脂MRI（WF-MRI）、定量CT（QCT）和双能X线吸收法（DXA）进行了验证。使用模拟骨髓不同成分的水和小链醇验证了基础材料组成框架。通过测量尸体椎骨中的脂肪细胞百分比并与DECT和WF-MRI进行比较来进行组织学验证。在一项I期试验中，16例妇科恶性肿瘤患者（接受了卵巢切除术、放疗或化疗）在治疗前和治疗后12个月接受了DECT、QCT、WF-MRI和DXA检查。对腰椎和右股骨颈的BMD和MF百分比及分布进行了量化。
测量精度（3mg/cm³）足以区分测试溶液。尸体骨组织学中的肥胖程度与使用DECT和WF-MRI测量的MF高度相关（分别为r = 0.80和0.77）。在临床试验中，DECT与WF-MRI显示出高度的总体相关性（r = 0.77，95%CI：0.69，0.83）。治疗后MF显著增加（p < 0.002）。化疗和放疗导致的MF增加比卵巢切除术更大（p < 0.032）。通过DECT测量，L4的BMD下降了14%，通过QCT下降了20%，但通过DXA仅下降了5%（所有p < 0.002）。在基线时，我们观察到MF与BMD之间存在统计学上显著的负相关，治疗后这种相关性显著减弱。
我们的研究表明，与WF-MRI类似，DECT可以准确测量骨髓肥胖程度。两种成像方式均显示癌症治疗后MF迅速增加。我们的结果表明，在癌症治疗后监测骨骼健康时，MF和BMD不能相互替代使用。
