Magnetic resonance studies from the last 10 years have conclusively demonstrated that choline metabolism is altered in a wide variety of cancers. In cancer, the choline metabolite profile is characterized by an elevation of phosphocholine and total choline-containing compounds. This elevation is increasingly being used as an endogenous biomarker of cancer. Importantly, the enzymes and pathways resulting in these distinct alterations in phosphocholine and total choline may provide novel molecular targets for specific, targeted anticancer therapies. In this article, we have summarized some of the magnetic resonance spectroscopy and positron emission tomography techniques that are currently available, or will be in the near future, for choline metabolism-based diagnosis, staging and therapy assessment in cancer patients. This review also outlines currently known molecular alterations that cause the aberrant choline metabolite profile in cancers and concludes with a summary of recent research findings that may, in the future, lead to novel anticancer therapies targeting choline metabolism.

Choline metabolism in cancer: implications for diagnosis and therapy

Recent technical advances in diffusion-weighted imaging (DWI) greatly enhanced the clinical value of magnetic resonance imaging (MRI) of the body. DWI can provide excellent tissue contrast based on molecular diffusion and may be able to demonstrate malignant tumors. Quantitative measurement of the apparent diffusion coefficient (ADC) may be valuable in distinguishing between malignant and benign lesions. We reviewed DWI and conventional MRI of the female pelvis to study the utility of DWI in patients with gynecological diseases. Although the ADC can help to differentiate between normal and cancerous tissue in the uterine cervix and endometrium, its utility may be limited by the large overlap of the uterine myometrium and ovaries. On the other hand, the ADC may be useful for monitoring the therapeutic outcome after uterine arterial embolizati (UAE), chemotherapy and/or radiation therapy. In patients with ovarian cancer, DWI demonstrates high intensity not only at the primary cancer site but also in disseminated peritoneal implants. When added to conventional MRI findings, DWI and ADC values provide additional information and DWI may play an important role in the diagnosis of patients with gynecological diseases.

Role of diffusion-weighted imaging in the diagnosis of gynecological diseases

Elevated interstitial fluid pressure (IFP) in tumors can cause metastatic dissemination and treatment resistance, but its study poses a challenge because of a paucity of noninvasive imaging strategies. In this study, we address this issue by reporting the development of a noninvasive tool to assess tumor IFP and interstitial hypertension-induced lymph node metastasis. Using mouse xenograft models of several types of human cancer, we used gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA) as a contrast agent for dynamic contrast-enhanced MRI (DCE-MRI). Immediately after Gd-DTPA administration, a high-signal-intensity rim was observed in the tumor periphery, which moved outward with time. Assuming the velocity of Gd-DTPA to be equal to the fluid flow velocity, we used a simple model of peritumoral interstitial fluid flow to calculate the fluid flow velocity at the tumor surface (v(0)) based on the rim movement. Significant positive correlations were found between v(0) and IFP in all tumor xenografts. Moreover, the primary tumors of metastasis-positive mice displayed higher IFP and v(0) than the primary tumors of metastasis-negative mice. Findings were confirmed in cervical cancer patients with pelvic lymph node metastases, where we found v(0) to be higher compared with patients without lymph node involvement (P < 0.00001). Together, these findings establish that Gd-DTPA-based DCE-MRI can noninvasively visualize tumor IFP, and they reveal the potential for v(0) determined by this method to serve as a novel general biomarker of tumor aggressiveness.

https://cancerres.aacrjournals.org/content/canres/72/19/4899.full.pdf

Interstitial Fluid Pressure and Associated Lymph Node Metastasis Revealed in Tumors by Dynamic Contrast-Enhanced MRI

Recent developments in MR techniques have magnified the roles and potential of MRI in the female pelvis. This article reviews the techniques and clinical applications of functional MRI (fMRI) of the female pelvis, including cine MRI, diffusion-weighted MRI (DWI), and dynamic contrast-enhanced (DCE)-MRI. Cine MRI is a useful tool for evaluating uterine contractility, including sustained contraction and peristalsis, in a variety of conditions and gynecologic disorders, and for evaluating pelvic-floor weakness. DWI can demonstrate abnormal signals in pathologic foci based on differences in molecular diffusion. It also enables the quantitative evaluation of the apparent diffusion coefficient (ADC), which may be useful for distinguishing malignant from benign tissues and monitoring therapeutic outcome. DCE-MRI has the potential to improve tumor detection and local staging, and can also provide quantitative information about perfusion of the tumor, which may be useful for both monitoring therapeutic effects and predicting therapeutic outcome. Understanding the roles played by functional MR techniques in the female pelvic region is beneficial not only for determining clinical applications, but also for developing further investigations with MRI.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmri.20913

Functional MR imaging of the female pelvis

In this article the role of MR imaging in the management of cervical cancer is reviewed and illustrated. The appearance of the normal uterine cervix and of cervical carcinoma is shown. Important factors for optimal MR imaging of cervical carcinoma are reviewed. The value of MR imaging in the staging of cervical carcinoma is illustrated by showing parametrial invasion and lymph node involvement. Finally, the value of MR imaging staging is compared with clinical staging, CT staging, and surgical findings. The role of new imaging techniques, such as fast dynamic enhanced MR imaging, is described.

The role of MR imaging in invasive cervical carcinoma.

Background: To identify the reasons for misdiagnosis of the degree of stromal invasion by uterine cervical cancer with various magnetic resonance sequences.
 
Methods: T2-weighted, dynamic, and postcontrast T1-weighted images were obtained in the sagittal plane in 20 patients with uterine cervical cancer. After evaluating these sequences for the degree of stromal invasion, histologic specimens were directly correlated with these images.
 
Results: The degree of stromal invasion was correctly diagnosed in 15 of the 20 cases on T2-weighted images, in 12 on dynamic images, and in eight on postcontrast T1-weighted images. All misdiagnoses were due to overestimation. Histologically, peritumoral stroma showed inflammation or edema in two patients, whereas no histological abnormality was found in the other patients. A hyperintense rim, i.e., a peritumoral enhanced ring-shaped structure, was observed on the enhanced images of five patients. The hyperintense rim corresponded to the periphery of the tumor in three patients and to the cervical stroma in two patients.
 
Conclusion: T2-weighted images permitted the most accurate evaluation of stromal invasion by uterine tumors. Overdiagnosis may be due to an abnormal intensity of the cervical stroma, which was observed more frequently on dynamic and postcontrast T1-weighted images than on T2-weighted images.

MR imaging of cervical carcinoma: comparison among T2-weighted, dynamic, and postcontrast T1-weighted images with histopathological correlation.

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MR imaging of cervical carcinoma: comparison among T2-weighted, dynamic, and postcontrast T1-weighted images with histopathological correlation.