Karimian-Jazi Kianush, Enbergs Noah, Golubtsov Evgeny, Schregel Katharina, Ungermann Johannes, Fels-Palesandro Hannah, Schwarz Daniel, Sturm Volker, Kernbach Julius M, Batra David, Ippen Franziska M, Pflüger Irada, von Knebel Doeberitz Nikolaus, Heiland Sabine, Bunse Lukas, Platten Michael, Winkler Frank, Wick Wolfgang, Paech Daniel, Bendszus Martin, Breckwoldt Michael O
From the Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany (K.K.-J., N.E., E.G., K.S., J.U., H.F.-P., D.S., V.S., J.M.K., I.P., S.H., M.B., M.O.B.); Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ), Heidelberg, Germany (K.K.-J., F.W., W.W.); Department of Neurology, Heidelberg University Hospital and National Center for Tumor Diseases (NCT), Heidelberg, Germany (D.B., F.M.I., F.W., W.W.); DKTK, DKFZ, Clinical Cooperation Unit Neuropathology, Heidelberg, Germany (F.M.I.); Division of Radiology, DKFZ, Heidelberg, Germany (N.V., D.P.); Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, DKTK, DKFZ, Heidelberg, Germany (L.B., M.P., M.O.B.); Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany (L.B., M.P.); Division of Neuroradiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.P.); and Clinic for Neuroradiology, University Hospital Bonn, Bonn, Germany (D.P.).
Invest Radiol. 2025 Jun 1;60(6):414-422. doi: 10.1097/RLI.0000000000001145. Epub 2024 Dec 9.
Recurrent glioma is highly treatment resistant due to its metabolic, cellular, and molecular heterogeneity and invasiveness. Tumor monitoring by conventional MRI has shortcomings to assess these key glioma characteristics. Recent studies introduced chemical exchange saturation transfer for metabolic imaging in oncology and assessed its diagnostic value for newly diagnosed glioma. This prospective study investigates amide proton transfer-weighted (APTw) MRI at 3 T as an imaging biomarker to elucidate the molecular heterogeneity and invasion patterns of recurrent glioma in comparison to pseudoprogression (PsPD).
We performed a monocenter, prospective trial and screened 371 glioma patients who received tumor monitoring between August 2021 and March 2024 at our institution. The study included IDH wildtype astrocytoma and IDH mutant astrocytoma and oligodendroglioma, graded according to the WHO 2021 classification. Patients had received clinical standard of care treatment including surgical resection and radiochemotherapy prior to study inclusion. Patients were monitored by 3 monthly MRI follow-up imaging, and response assessment was performed according to the RANO criteria. Within this cohort, we identified 30 patients who presented with recurrent glioma and 12 patients with PsPD. In addition to standard anatomical sequences (FLAIR and T1-w Gd-enhanced sequences), MRI included APTw imaging. After sequence co-registration, semiautomated segmentation was performed of the FLAIR lesion, CE lesion, resection cavity, and the contralateral normal-appearing white matter, and APTw signals were quantified in these regions of interest.
APTw values were highest in solid, Gd-enhancing tumor parts as compared with the nonenhancing FLAIR lesion (APTw: 1.99% vs 1.36%, P = 0.001), whereas there were no detectable APTw alterations in the normal-appearing white matter (APTw: 0.005%, P < 0.001 compared with FLAIR). Patients with progressive disease had higher APTw levels compared with patients with PsPD (APTw: 1.99% vs 1.26%, P = 0.008). Chemical exchange saturation transfer identified heterogeneity within the FLAIR lesion that was not detectable by conventional sequences. There were also focal APTw signal peaks within contrast enhancing lesions as putative metabolic hotspots within recurrent glioma. The resection cavity developed an APTw increase at recurrence that was not detectable prior to recurrence nor in patients with PsPD (APTw before recurrence: 0.6% vs 2.68% at recurrence, P = 0.03).
Our study shows that APTw imaging can differentiate PD and PsPD. We identify previously undetectable imaging patterns during glioma recurrence, which include alterations within resection cavity associated with disease progression. Our work highlights the clinical potential of APTw imaging for glioma monitoring and further establishes it as an imaging biomarker in neuro-oncology.
复发性胶质瘤因其代谢、细胞和分子异质性及侵袭性而具有高度治疗抵抗性。传统MRI进行肿瘤监测在评估这些关键的胶质瘤特征方面存在不足。最近的研究引入了化学交换饱和转移用于肿瘤学中的代谢成像，并评估了其对新诊断胶质瘤的诊断价值。本前瞻性研究调查3T场强下的酰胺质子转移加权（APTw）MRI作为一种成像生物标志物，以阐明复发性胶质瘤与假性进展（PsPD）相比的分子异质性和侵袭模式。
我们进行了一项单中心前瞻性试验，筛查了2021年8月至2024年3月在我们机构接受肿瘤监测的371例胶质瘤患者。该研究包括IDH野生型星形细胞瘤、IDH突变型星形细胞瘤和少突胶质细胞瘤，根据世界卫生组织2021年分类进行分级。患者在纳入研究前已接受包括手术切除和放化疗在内的临床标准治疗。患者每3个月接受一次MRI随访成像，并根据RANO标准进行疗效评估。在这个队列中，我们确定了30例出现复发性胶质瘤的患者和12例假性进展患者。除了标准解剖序列（液体衰减反转恢复序列和T1加权钆增强序列）外，MRI还包括APTw成像。序列配准后，对液体衰减反转恢复序列病变、钆增强病变、切除腔和对侧正常白质进行半自动分割，并在这些感兴趣区域量化APTw信号。
与未增强的液体衰减反转恢复序列病变相比，实性、钆增强肿瘤部分的APTw值最高（APTw：1.99%对1.36%，P = 0.001），而在正常白质中未检测到APTw改变（APTw：0.005%，与液体衰减反转恢复序列相比P < 0.001）。疾病进展患者的APTw水平高于假性进展患者（APTw：1.99%对1.26%，P = 0.008）。化学交换饱和转移识别出液体衰减反转恢复序列病变内传统序列无法检测到的异质性。在对比增强病变内也有局灶性APTw信号峰，作为复发性胶质瘤内假定的代谢热点。切除腔在复发时出现APTw增加，在复发前及假性进展患者中均未检测到（复发前APTw：0.6%对复发时2.68%，P = 0.03）。
我们的研究表明，APTw成像可以区分疾病进展和假性进展。我们识别出胶质瘤复发期间以前未检测到的成像模式，包括与疾病进展相关的切除腔内改变。我们的工作突出了APTw成像在胶质瘤监测中的临床潜力，并进一步将其确立为神经肿瘤学中的一种成像生物标志物。
