Chemical Exchange Saturation Transfer Magnetic Resonance Imaging for Longitudinal Assessment of Intracerebral Hemorrhage and Deferoxamine Treatment at 3T in a Mouse Model

Abstract

BACKGROUND: Noninvasive imaging of molecular alterations after intracerebral hemorrhage (ICH) could provide valuable information to guide and monitor treatments. Chemical exchange saturation transfer (CEST) magnetic resonance imaging has demonstrated promises in identifying proliferation, necrosis, and changes in cellularity in brain tumors. Here, we applied CEST magnetic resonance imaging to monitor molecular changes in hematoma without and with treatment noninvasively over 2 weeks at 3T using endogenous contrast. METHODS: CEST contrast related to proteins at 3.5 ppm (amide proton transfer) and proteins/lipids at −3.5 ppm (relayed nuclear overhauser effect [rNOE]) were examined over 14 days in a collagenase-induced ICH mouse model. Imaging findings were validated with immunohistochemistry based on the ICH neuropathology. We also examined iron-containing phantoms that mimicked iron concentrations in hematoma to ensure the iron will not attenuate the CEST contrast during disease progression. Based on the validity of the CEST contrast of hematoma, we further examined related molecular alterations under iron-chelation treatment with deferoxamine. RESULTS: We observed the temporal and spatial differences of CEST contrasts between rNOE at −3.5 ppm and amide proton transfer at 3.5 ppm, in which the core and perihematoma could be identified by rNOE on day 3 and day 14, and amide proton transfer on day 1, day 7, and day 14. Moreover, we observed a 25.7% significant reduction ( P <0.05) of rNOE contrast after deferoxamine treatment to the ICH mice on day 3, which was not observable in amide proton transfer contrast. Our histology data indicated that rNOE primarily correlated with the myelin pathology, and amide proton transfer could reflect the cellularity increase at hematoma up to day 7. CONCLUSIONS: Significant rNOE changes correlated well with histologic findings, especially myelin lipids, and regional characteristics in hematoma indicate the uniqueness of CEST magnetic resonance imaging in monitoring molecular changes during ICH and treatment.

Post-Surgical Depositions of Blood Products Are No Major Confounder for the Diagnostic and Prognostic Performance of CEST MRI in Patients with Glioma

“…In previous studies, Sawaya et al, Wang et al and Ma et al observed that asymmetry-based APTw imaging showed markedly elevated contrast values in rat models and in patients with acute and subacute cerebral bleeding, which very likely corresponded to accumulations of deoxygenized hemoglobin and mHb [ 13 , 19 , 20 , 34 , 35 , 36 ]. Lai et al, on the other hand, observed significantly reduced contrast values in the subacute stage of cerebral hemorrhage in a preclinical study, using an apparent exchange-dependent relaxation compensated metric of the APT (APT AREX ) [ 21 ]. Contrary to these findings, to our knowledge, there are no available published results on the CEST contrast behaviors of Hs.…”

“…For this reason, mHb and Hs not only have a strong influential impact on T 1 and T 2 , but should also contribute to the APT and ssMT pool. However, whilst several groups have demonstrated that CEST imaging of the APT can differentiate between acute and subacute stages of intracranial hemorrhage [ 19 , 20 , 21 ], little is known about the influence of mHb and Hs on the clinical performance of APT and ssMT imaging in patients with glioma in the post-radiotherapy interval. Furthermore, CEST contrasts are heavily dependent on the metrics used for their reconstruction form the Z-spectrum [ 7 , 22 , 23 ].…”

Deep‐learning‐based super‐resolution for accelerating chemical exchange saturation transfer MRI

“…Chemical exchange saturation transfer (CEST) MRI is a molecular imaging approach that enables the visualization of physiological environment in tissues by harnessing exchangeable protons in biomolecules as contrast agents. [1][2][3][4] By detecting these protons in an increasing library of biomolecules, which includes glucose, [5][6][7][8][9] mobile proteins and peptides, 10,11 lactate, 12 creatine, [13][14][15] glycogen, 16 and other metabolites, with high sensitivity and specificity, CEST MRI has shown promising clinical applications in disease diagnosis and guided treatment for many neurological diseases, including Alzheimer's disease (AD), 8,17 multiple sclerosis, [18][19][20][21] stroke, [22][23][24] and cancer. [25][26][27][28] For example, it has been demonstrated as a unique approach to differentiate tumor recurrence from radiation necrosis using the amide proton of proteins and peptides in cancer, which cannot be easily identify by other neuroimaging technologies.…”

Novel Nanoprobe with Combined Ultrasonography/Chemical Exchange Saturation Transfer Magnetic Resonance Imaging for Precise Diagnosis of Tumors

“…Over the past decade, Chemical Exchange Saturation Transfer Technology (CEST) MRI techniques have attracted interest as a robust imaging approach for probing molecular imaging changes in vivo [ 14 , 15 , 16 , 17 , 18 ]. CEST is a new MRI approach based on the theory of magnetization transfer (MT) and chemical exchange.…”