The Continuing Evolution of Molecular Functional Imaging in Clinical Oncology: The Road to Precision Medicine and Radiogenomics (Part II).

The present era of precision medicine sees "cancer" as a consequence of molecular derangements occurring at the commencement of the disease process, with morphological changes happening much later in the process of tumourigenesis. Conventional imaging techniques, such as computed tomography (CT), ultrasound (US) and magnetic resonance imaging (MRI) play an integral role in the detection of disease at the macroscopic level. However, molecular functional imaging (MFI) techniques entail the visualisation and quantification of biochemical and physiological processes occurring during tumourigenesis. MFI has the potential to play a key role in heralding the transition from the concept of "one-size-fits-all" treatment to "precision medicine". Integration of MFI with other fields of tumour biology such as genomics has spawned a novel concept called "radiogenomics", which could serve as an indispensable tool in translational cancer research. With recent advances in medical image processing, such as texture analysis, deep learning and artificial intelligence, the future seems promising; however, their clinical utility remains unproven at present. Despite the emergence of novel imaging biomarkers, the majority of these require validation before clinical translation is possible. In this two part review, we discuss the systematic collaboration across structural, anatomical and molecular imaging techniques that constitute MFI. Part I reviews positron emission tomography, radiogenomics, AI, and optical imaging, while part II reviews MRI, CT and ultrasound, their current status, and recent advances in the field of precision oncology.

Correction to: The Continuing Evolution of Molecular Functional Imaging in Clinical Oncology: The Road to Precision Medicine and Radiogenomics (Part II).

An Online First version of this article was made available online at http://link.springer.com/journal/40291/onlineFirst/page/1 on 01 Nov 2018. An error was subsequently identified in the article, and the following correction should be noted.

Role of 3T multiparametric-MRI with BOLD hypoxia imaging for diagnosis and post therapy response evaluation of postoperative recurrent cervical cancers.

OBJECTIVES: To assess the diagnostic value of multiparametric-MRI (MPMRI) with hypoxia imaging as a functional marker for characterizing and detecting vaginal vault/local recurrence following primary surgery for cervical cancer. METHODS: With institutional review board approval and written informed consent 30 women (median age: 45 years) from October 2009 to March 2010 with previous operated carcinoma cervix and suspected clinical vaginal vault/local recurrence were examined with 3.0T-MRI. MRI imaging included conventional and MPMRI sequences [dynamic contrast enhanced (DCE), diffusion weighted (DW), 1H-MR spectroscopy (1HMRS), blood oxygen level dependent hypoxia imaging (BOLD)]. Two radiologists, blinded to pathologic findings, independently assessed the pretherapy MRI findings and then correlated it with histopathology findings. Sensitivity, specificity, positive predictive value, negative predictive value and their confidence intervals were calculated. The pre and post therapy conventional and MPMRI parameters were analyzed and correlated with response to therapy. RESULTS: Of the 30 patients, there were 24 recurrent tumors and 6 benign lesions. The accuracy of diagnosing recurrent vault lesions was highest at combined MPMRI and conventional MRI (100%) than at conventional-MRI (70%) or MPMRI (96.7%) alone. Significant correlation was seen between percentage tumor regression and pre-treatment parameters such as negative enhancement integral (NEI) (p = 0.02), the maximum slope (p = 0.04), mADC value (p = 0.001) and amount of hypoxic fraction on the pretherapy MRI (p = 0.01). CONCLUSION: Conventional-MR with MPMRI significantly increases the diagnostic accuracy for suspected vaginal vault/local recurrence. Post therapy serial MPMRI with hypoxia imaging follow-up objectively documents the response. MPMRI and BOLD hypoxia imaging provide information regarding tumor biology at the molecular, subcellular, cellular and tissue levels and this information may be used as an appropriate and reliable biologic target for radiation dose painting to optimize therapy in future.

Bench to bedside molecular functional imaging in translational cancer medicine: to image or to imagine?

Ongoing research on malignant and normal cell biology has substantially enhanced the understanding of the biology of cancer and carcinogenesis. This has led to the development of methods to image the evolution of cancer, target specific biological molecules, and study the anti-tumour effects of novel therapeutic agents. At the same time, there has been a paradigm shift in the field of oncological imaging from purely structural or functional imaging to combined multimodal structure-function approaches that enable the assessment of malignancy from all aspects (including molecular and functional level) in a single examination. The evolving molecular functional imaging using specific molecular targets (especially with combined positron-emission tomography [PET] computed tomography [CT] using 2- [(18)F]-fluoro-2-deoxy-D-glucose [FDG] and other novel PET tracers) has great potential in translational research, giving specific quantitative information with regard to tumour activity, and has been of pivotal importance in diagnoses and therapy tailoring. Furthermore, molecular functional imaging has taken a key place in the present era of translational cancer research, producing an important tool to study and evolve newer receptor-targeted therapies, gene therapies, and in cancer stem cell research, which could form the basis to translate these agents into clinical practice, popularly termed "theranostics". Targeted molecular imaging needs to be developed in close association with biotechnology, information technology, and basic translational scientists for its best utility. This article reviews the current role of molecular functional imaging as one of the main pillars of translational research.

Osteoradionecrosis of the mandible: through a radiologist's eyes.

Head and neck malignancies constitute a major cause of morbidity and mortality all over the world. Radiotherapy plays a pivotal role in the management of these tumours; however, it has associated complications, with mandibular osteoradionecrosis (ORN) being one of the gravest orofacial complications. Early diagnosis, extent evaluation, and detection of complications of ORN are imperative for instituting an appropriate management protocol. ORN can closely mimic tumour recurrence, the differentiation of which has obvious clinical implications. The purpose of the present review is to acquaint the radiologist with the imaging features of mandibular ORN and the ways to differentiate ORN from tumour recurrence.

Endometrial polyps associated with endometrial hyperplasia in an obese bonnet monkey (Macaca radiata): a case report.

BACKGROUND: A 10-year-old, female bonnet monkey (Macaca radiata) showed abnormal menstrual cycle length with heavy menstrual bleeding for 6-8 days. METHODS: Uterine ultrasound and histological examinations of endometrium by endometrial biopsy. RESULTS: An ultrasound examination of the uterine cavity showed presence of an enlarged polypoid mass. Further endometrial histology confirmed the presence of simple endometrial hyperplasia. CONCLUSIONS: We report for the first time that endometrial polyp is associated with endometrial hyperplasia in obese bonnet monkey.

Transrectal ultrasound-guided biopsy of recurrent cervical carcinoma.

The objective of this study was to evaluate the feasibility, safety and diagnostic accuracy of transrectal ultrasound (TRUS)-guided core biopsy for recurrent carcinoma of the uterine cervix in patients with non-diagnostic vaginal cytology and transvaginal punch biopsy.17 patients with clinical and imaging suspicion of recurrent carcinoma of the cervix, and with negative cytology and punch biopsy, were referred for TRUS-guided biopsy of a recurrent mass. Data were collected with respect to demography, previous diagnosis, treatment received, size and location of the recurrent lesion, and biopsy results. Adequate samples were obtained for all patients. TRUS-guided biopsy was technically successful in all of the patients and provided histological diagnosis of recurrence in 16 patients. One of the patients had post-radiation fibrosis. There were no procedure-related complications. In conclusion, TRUS-guided biopsy for recurrent cervical cancer is a feasible, safe and accurate method for establishing a histopathological diagnosis. It should be considered in patients with non-diagnostic vaginal cytology and punch biopsy.

Choroidal metastasis from non-seminomatous germ cell tumour of the testis.

Ureal metastases (although an uncommon site of metastatic involvement) are seen with primary tumours of the lung and breast and, very rarely, in other primary tumours. Undescended testis predisposes to malignancy. We present a rare case of choroidal metastasis from a non-seminomatous germ cell tumour arising in an undescended testis, and describe its clinical, ultrasound and MRI findings together with a relevant review of the literature.

Primary rhabdomyosarcoma of the seminal vesicle.

Sarcomas of the seminal vesicle are very rare and poorly documented; as it is not always possible to pinpoint a truly vesicular origin of the pelvic mass due to local spread at the time of presentation. The purpose of the article is to document and characterize a rhabdomyosarcoma of the seminal vesicle of which to the knowledge of the authors there has been no previous report in the English literature.

Role of ultrasonography to detect axillary node involvement in operable breast cancer.

Prompted by the concern about unnecessary axillary dissections, we prospectively studied the accuracy of clinical examination (CE) and conventional ultrasonography (USG, 7.5 MHz), to diagnose pre-operatively metastatic axillary lymph nodes in 200 operable breast cancer patients. USG had higher specificity (90% vs 77%, P = 0.025) and higher positive predictive value (ppv = 90% vs 76%, P = 0.02) than CE. Together, CE + USG had higher sensitivity (82% vs 58%, P = 0.00005) and higher negative predictive value (npv = 76% vs 58%, P = 0.008) than CE alone. In women < 45 years, CE + USG had higher sensitivity (91% vs 76%, P = 0.037) and npv (89% vs 67%, P = 0.018) than in older women. The sensitivity and npv of CE + USG to detect > 1 positive node were 97% (for both) in women < 45 years compared to 81% and 79% in older women. The high sensitivity of CE + USG (82% for the whole group) is probably due to the higher proportion of young women (median age = 45) in our population. It suggests that using CE + USG to avoid axillary dissection in some patients is feasible.