In recent years, several key advances in the management of locally advanced rectal cancer have been made, including the implementation of total mesorectal excision as the standard surgical approach; use of neoadjuvant chemoradiotherapy in selected patients with a high risk of local recurrence, and finally, adoption of organ preservation strategies, through either local excision or nonoperative management in selected patients with clinical complete response following neoadjuvant chemoradiotherapy. This review aims to shed light on the role of rectal MRI in the assessment of treatment response after neoadjuvant therapy, which is especially important given the growing feasibility of nonoperative management. First, an overview of current neoadjuvant therapies and response assessment based on digital rectal examination, endoscopy, and MRI will be provided. Second, the use of a high-quality restaging rectal MRI protocol will be presented. Third, a step-by-step approach to assessing treatment response on restaging rectal MRI following neoadjuvant treatment will be outlined, acknowledging challenges faced by radiologists during MRI interpretation. Finally, research related to response assessment will be discussed. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.

The aim of this study was to develop and validate a nomogram model to evaluate lymph node metastasis (LNM) in patients with rectal cancer (RC).

A total of 162 patients with RC were included in the study. The MRI reported model, the Radscore model, and the Complex model were constructed using the logistics regression (LR) algorithm. The DeLong test and decision curve analysis (DCA) were used to compare the prediction performance and clinical utility of these models. The nomogram model was constructed to visualize the prediction results of the best model. Model performance was evaluated in the training and validation groups, and the calibration curve and Hosmer-Lemeshow goodness of fit test were used to evaluate the calibration.

All three models constructed by the LR algorithm were good at identifying LNM. The DeLong test and the DCA results showed that the Complex model outperformed the MRI reported model and the Radscore model in relation to their predictive performance and clinical utility. The nomogram of the Complex model had an area under the curve (AUC) of 0.902 (95% confidence interval (CI) 0.848-0.957) in the training group and an AUC of 0.891 (95% CI 0.799-0.983) in the validation group. Meanwhile, the nomogram showed good calibration.

The nomogram model constructed based on T2WI radiomics and MRI reported had good diagnostic efficacies for LNM in patients with RC, and provided a new auxiliary method for accurate and individualized clinical management.

Response Evaluation Criteria in Solid Tumors (RECIST) is the gold standard for assessment of treatment response in solid tumors. Morphologic change of tumor size evaluated by RECIST is often correlated with survival length and has been considered as a surrogate endpoint of therapeutic efficacy. However, the detection of morphologic change alone may not be sufficient for assessing response to new anti-cancer medication in all solid tumors. During the past fifteen years, several molecular-targeted therapies and immunotherapies have emerged in cancer treatment which work by disrupting signaling pathways and inhibited cell growth. Tumor necrosis or lack of tumor progression is associated with a good therapeutic response even in the absence of tumor shrinkage. Therefore, the use of unmodified RECIST criteria to estimate morphological changes of tumor alone may not be sufficient to estimate tumor response for these new anti-cancer drugs. Several studies have reported the low reliability of RECIST in evaluating treatment response in different tumors such as hepatocellular carcinoma, lung cancer, prostate cancer, brain glioma, bone metastasis, and lymphoma. There is an increased need for new medical imaging biomarkers, considering the changes in tumor viability, metabolic activity, and attenuation, which are related to early tumor response. Promising imaging techniques, beyond RECIST, include dynamic contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI), diffusion-weight imaging (DWI), magnetic resonance spectroscopy (MRS), and ¹⁸ F-fluorodeoxyglucose (FDG) positron emission tomography (PET). This review outlines the current RECIST with their limitations and the new emerging concepts of imaging biomarkers in oncology.

Photo-thermal therapy (PTT) has been at the center of attention as a new method for cancer treatment in recent years. It is important to predict the response to treatment in the PTT procedure. Using magnetic resonance spectroscopy (MRS) can be considered a novel technique in evaluating changes in metabolites resulted from PTT.

In the present project, we conducted an in vivo study to assess the efficacy of ¹H-MRS as a noninvasive technique to evaluate the response to treatment in the early hours following PTT. The BALB/c mice subcutaneously bearing tumor cells (CT26 cell line) were scanned by ¹H-MRS before and after PTT. Iron oxide-gold core-shell (Fe₃O₄@Au) as PTT agent was injected into intra-peritoneal at first and then irradiated by NIR laser. Single-voxel Point RESolved Spectroscopy (PRESS) sequence (TE = 144) was used, and metabolites alternations were evaluated by the non-parametric Wilcoxon test. Besides, Nanoparticle (NP) relaxometry was conducted for negative contrast agents' potentials.

MRS choline (Cho) peak dramatically reduced 24 h post-PTT (p = 0.01) and lipid peak as a marker for necrosis of tumor elevated (p = 0.01) just in group 3 (NPs injection + laser irradiation) 24 h after the procedure.

¹H-MRS showed its potential as a method in detecting the changes in metabolites and revealing the outcome accurately. Response to photo-thermal therapy evaluation was achievable only one day after PTT and proved by a 10-day follow-up of the tumor size. Iron oxide-gold core-shell can also be used as a negative contrast agent in MRI images during therapy.

Nanotechnology-based photothermal therapy (NPTT) is a new emerging modality of cancer therapy. To have the right prediction and early detection of response to NPTT, it is necessary to get rapid feedback from a tumor treated by NPTT procedure and stay informed of what happens in the tumor site. We performed this study to find if proton magnetic resonance spectroscopy (1H-MRS) can be well responsive to such an imperative requirement. We considered various treatment groups including gold nanoparticles (AuNPs), laser, and the combination of AuNPs and laser (NPTT group). Therapeutic effects on CT26 colon tumor-bearing BALB/c mice were studied by looking at alterations that happened in 1H-MRS signals and tumor size after conducting treatment procedures. In MRS studies, the alterations of choline and lipid concentrations and their ratio were investigated. Having normalized the metabolite peak to water peak, we found a significant decrease in choline concentration post-NPTT (from (1.25 ± 0.05) × 10^-3 to (0.43 ± 0.04) × 10^-3), while the level of lipid concentration in the tumor was slightly increased (from (2.91 ± 0.23) × 10^-3 to (3.52 ± 0.31) × 10^-3). As a result, the choline/lipid ratio was significantly decreased post-NPTT (from 0.41 ± 0.11 to 0.11 ± 0.02). Such alterations appeared just 1 day after NPTT. Tumor shrinkage in all groups was studied and significant changes were significantly detectable on day 7 post-NPTT procedure. In conclusion, the study of choline/lipid ratio using 1H-MRS may help us estimate what happens in a tumor treated by the NPTT method. Such an in vivo assessment is interestingly feasible as soon as just 1 day post-NPTT. This would undoubtedly help the oncologists make a more precise decision about treatment planning strategies. Monitoring of the choline/lipid ratio by ¹H-MRS can be helpful for prediction and early detection of response to nano-photo-thermal therapy.

Colorectal cancer (CRC) represents one of the leading causes of tumor-related deaths worldwide. Among the various tools at physicians' disposal for the diagnostic management of the disease, tomographic imaging (e.g., CT, MRI, and hybrid PET imaging) is considered essential. The qualitative and subjective evaluation of tomographic images is the main approach used to obtain valuable clinical information, although this strategy suffers from both intrinsic and operator-dependent limitations. More recently, advanced imaging techniques have been developed with the aim of overcoming these issues. Such techniques, such as diffusion-weighted MRI and perfusion imaging, were designed for the "in vivo" evaluation of specific biological tissue features in order to describe them in terms of quantitative parameters, which could answer questions difficult to address with conventional imaging alone (e.g., questions related to tissue characterization and prognosis). Furthermore, it has been observed that a large amount of numerical and statistical information is buried inside tomographic images, resulting in their invisibility during conventional assessment. This information can be extracted and represented in terms of quantitative parameters through different processes (e.g., texture analysis). Numerous researchers have focused their work on the significance of these quantitative imaging parameters for the management of CRC patients. In this review, we aimed to focus on evidence reported in the academic literature regarding the application of parametric imaging to the diagnosis, staging and prognosis of CRC while discussing future perspectives and present limitations. While the transition from purely anatomical to quantitative tomographic imaging appears achievable for CRC diagnostics, some essential milestones, such as scanning and analysis standardization and the definition of robust cut-off values, must be achieved before quantitative tomographic imaging can be incorporated into daily clinical practice.

The objective of this study was to investigate the incidence and clinical significance of intratumoral fat deposition in colorectal liver metastases (CLMs) after preoperative chemotherapy using dual-echo gradient-recalled echo MRI.

Our institutional review board approved this retrospective radiographic study and waived the requirement for informed patient consent. Fifty-nine patients (33 men, 26 women; median age, 62 years old) who underwent preoperative MRI and curative hepatic resection for colorectal liver metastases after chemotherapy were selected. Twenty patients also underwent MRI before chemotherapy. On dual-echo gradient-recalled echo MR images, intratumoral fat deposition and fat signal fraction at the densest areas of fat deposition in colorectal liver metastases were evaluated. Predictors of overall survival and intratumoral fat deposition after chemotherapy were identified by multivariate analyses.

Before and after chemotherapy, 0 (0%) and 32 (54%) of the patients exhibited intratumoral fat deposition, respectively. Independent predictors of poor overall survival were presence of five or more CLMs (p < 0.001), fat signal fraction of 12% or more (p = 0.01), age of 65 years or older (p = 0.02), and tumor response classified as progressive or stable disease by the Response Evaluation Criteria in Solid Tumors 1.1 (p = 0.049). Predictors of tumor fat signal fraction being 12% or greater after chemotherapy were largest tumor size of 5 cm or more (p = 0.005), tumor calcification (p = 0.008), and history of cetuximab or panitumumab administration (p = 0.04).

CLMs after preoperative chemotherapy frequently exhibit intratumoral fat deposition.

Imaging techniques are clinical decision-making tools in the evaluation of patients with colorectal cancer (CRC). The aim of this article is to discuss the potential of recent advances in imaging for diagnosis, prognosis, therapy planning, and assessment of response to treatment of CRC. Recent developments and new clinical applications of conventional imaging techniques such as virtual colonoscopy, dual-energy spectral computed tomography, elastography, advanced computing techniques (including volumetric rendering techniques and machine learning), magnetic resonance (MR) imaging-based magnetization transfer, and new liver imaging techniques, which may offer additional clinical information in patients with CRC, are summarized. In addition, the clinical value of functional and molecular imaging techniques such as diffusion-weighted MR imaging, dynamic contrast material-enhanced imaging, blood oxygen level-dependent imaging, lymphography with contrast agents, positron emission tomography with different radiotracers, and MR spectroscopy is reviewed, and the advantages and disadvantages of these modalities are evaluated. Finally, the future role of imaging-based analysis of tumor heterogeneity and multiparametric imaging, the development of radiomics and radiogenomics, and future challenges for imaging of patients with CRC are discussed. Online supplemental material is available for this article. ^©RSNA, 2018.

In vivo NMR spectroscopy is known as magnetic resonance spectroscopy (MRS). MRS has been applied as both a research and a clinical tool in order to detect visible or nonvisible abnormalities. The adaptability of MRS allows a technique that can probe a wide variety of metabolic uses across different tissues. Although MRS is mostly applied for brain tissue, it can be used for detection, localization, staging, tumour aggressiveness evaluation, and tumour response assessment of breast, prostate, hepatic, and other cancers. In this article, the medical applications of MRS in the brain, including tumours, neural and psychiatric disorder studies, breast, prostate, hepatic, gastrointestinal, and genitourinary investigations have been reviewed.

Despite advances in multimodality treatment strategies for locally advanced rectal cancer and improvements in locoregional control, there is still a considerable variation in response to neoadjuvant chemoradiotherapy (CRT). Accurate prediction of response to neoadjuvant CRT would enable early stratification of management according to good responders and poor responders, in order to adapt treatment to improve therapeutic outcomes in rectal cancer. Clinical studies in diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI have shown promising results for the prediction of therapeutic response in rectal cancer. DWI allows for assessment of tumour cellularity. DCE-MRI enables evaluation of factors of the tumour microvascular environment and changes in perfusion in response to treatment. Studies have demonstrated that predictors of good response to CRT include lower tumour pre-CRT apparent diffusion coefficient (ADC), greater percentage increase in ADC during and post CRT, and higher pre-CRT K^trans. However, the mean ADC and K^trans values do not adequately reflect tumour heterogeneity. Multiparametric MRI using quantitative DWI and DCE-MRI in combination, and a histogram analysis technique can assess tumour heterogeneity and its response to treatment. This strategy has the potential to improve the accuracy of therapeutic response prediction in rectal cancer and warrants further investigation.

Abnormal metabolism is a key tumor hallmark. Proton magnetic resonance spectroscopy (1H-MRS) allows measurement of metabolite concentration that can be utilized to characterize tumor metabolic changes. 1H-MRS measurements of specific metabolites have been implemented in the clinic. This article performs a systematic review of image acquisition and interpretation of 1H-MRS for cancer evaluation, evaluates its strengths and limitations, and correlates metabolite peaks at 1H-MRS with diagnostic and prognostic parameters of cancer in different tumor types.

Magnetic resonance spectroscopy (MRS) is a noninvasive functional technique to evaluate the biochemical behavior of human tissues. This property has been widely used in assessment and therapy monitoring of brain tumors. MRS studies can be implemented outside the brain, with successful and promising results in the evaluation of prostate and breast cancer, although still with limited reproducibility. As a result of technical improvements, malignancies of the musculoskeletal system and abdominopelvic organs can benefit from the molecular information that MRS provides. The technical challenges and main applications in oncology of (1)H MRS in a clinical setting are the focus of this review.

Imaging techniques play a key role in the management of patients with colorectal cancer. The introduction of new advanced anatomical, functional, and molecular imaging techniques may improve the assessment of diagnosis, prognosis, planning therapy, and assessment of response to treatment of these patients. Functional and molecular imaging techniques in clinical practice may allow the assessment of tumour-specific characteristics and tumour heterogeneity. This paper will review recent developments in imaging technologies and the evolving roles for these techniques in colorectal cancer.

• Imaging techniques play a key role in the management of patients with colorectal cancer. • Advanced imaging techniques improve the evaluation of these patients. • Functional and molecular imaging allows assessment of tumour hallmarks and tumour heterogeneity.

The underglycosylated mucin 1 tumor antigen (uMUC1) is a biomarker that forecasts the progression of adenocarcinomas. In this study, we evaluated the utility of a dual-modality molecular imaging approach based on targeting uMUC1 for monitoring chemotherapeutic response in a transgenic murine model of pancreatic cancer (KCM triple transgenic mice). An uMUC1-specific contrast agent (MN-EPPT) was synthesized for use with magnetic resonance imaging (MRI) and fluorescence optical imaging. It consisted of dextran-coated iron oxide nanoparticles conjugated to the near infrared fluorescent dye Cy5.5 and to a uMUC1-specific peptide (EPPT). KCM triple transgenic mice were given gemcitabine as chemotherapy while control animals received saline injections following the same schedule. Changes in uMUC1 levels following chemotherapy were monitored using T2-weighted MRI and optical imaging before and 24 hr after injection of the MN-EPPT. uMUC1 expression in tumors from both groups was evaluated by histology and qRT-PCR. We observed that the average delta-T2 in the gemcitabine-treated group was significantly reduced compared to the control group indicating lower accumulation of MN-EPPT, and correspondingly, a lower level of uMUC1 expression. In vivo optical imaging confirmed the MRI findings. Fluorescence microscopy of pancreatic tumor sections showed a lower level of uMUC1 expression in the gemcitabine-treated group compared to the control, which was confirmed by qRT-PCR. Our data proved that changes in uMUC1 expression after gemcitabine chemotherapy could be evaluated using MN-EPPT-enhanced in vivo MR and optical imaging. These results suggest that the uMUC1-targeted imaging approach could provide a useful tool for the predictive assessment of therapeutic response.

Magnetic resonance imaging (MRI) has in recent years progressively established itself as one of the most valuable modalities for the diagnosis, staging and response assessment of rectal cancer and its use has largely focused on accurate morphological assessment. The potential of MRI, however, extends beyond detailed anatomical depiction: aspects of tissue physiology, such as perfusion, oxygenation and water molecule diffusivity, can be assessed indirectly. Functional MRI is rapidly evolving as a promising non-invasive assessment tool for tumour phenotyping and assessment of response to new therapeutic agents. In spite of promising experimental data, the evidence base for the application of functional MRI techniques in rectal cancer remains modest, reflecting the relatively poor agreement on technical protocols, image processing techniques and quantitative methodology to date, hampering routine integration into clinical management. This overview outlines the established strengths and the critical limitations of anatomical MRI in rectal cancer; it then introduces some of the functional MRI techniques and quantitative analysis methods that are currently available, describing their applicability in rectal cancer and reviewing the relevant literature; finally, it introduces the concept of a multi-parametric quantitative approach to rectal cancer.

Guidelines recommend MRI as part of the staging work-up of patients with rectal cancer because it can identify high-risk groups requiring preoperative treatment. Phenomenal tumour responses have been observed with current chemoradiotherapy regimens-even complete regression in 25% of patients. For these patients, the options of organ-saving treatment as an alternative to surgery are now discussed, and critical for this approach is the availability of tools that can accurately measure response. The value of MRI in rectal cancer staging is established, but the role of MRI for the selection of patients for organ-saving treatment is debatable, because MRI is not able to accurately assess tumour response to preoperative chemoradiotherapy (owing to its reliance on morphological changes). Functional MRI is emerging in the field of oncology. It combines information on detailed anatomy with that of tumour biology, providing comprehensive information on tumour heterogeneity and its changes as a result of treatment. This Review provides knowledge on the strengths and weaknesses of MRI for response assessment after chemoradiotherapy in rectal cancer and on its ability to predict tumour response at the time of primary diagnosis. It elaborates on new functional magnetic resonance technology and discusses whether this and new postprocessing approaches have the potential to improve prediction and assessment of response.

Functional imaging techniques enable physiological information to be derived, which, combined with high-resolution anatomical imaging, has the potential to improve the management of patients with intestinal disease. Two of the common pathologies where imaging has a substantial role in depicting disease extent, in staging disease, and assessing therapeutic response and/or disease relapse are cancer and inflammatory bowel disease. In these scenarios, functional imaging may augment assessment of disease activity, therapeutic response/non-response, as well as disease relapse by indicating physiological changes as a result of tumor, inflammation, or fibrosis.

Proton Magnetic Resonance Spectroscopy (1H MRS) is used for clinical diagnosis in some tumours. The aim of this study is to explore ex vivo the potential of 1H MRS in identifying malignancy through metabolic markers in the perspective of its application in all cases of difficult diagnosis and after neoadjuvant treatment.

Spectroscopy was performed ex vivo on 29 colorectal specimens. All patients were staged with imaging, underwent radical surgery and then followed-up. Spectral quantification analysis of components expressed in colorectal tumours and in healthy mucosa were evaluated. The MRS-tumour marker (MRS-tm) was calculated for each case. The U-test was used to compare MRS-tm in tumours and in healthy mucosa. In order to select a cut-off for MRS-tm in the tumour and healthy mucosa and to distinguish patients who were disease-free or with recurrence-progression, we performed the ROC curve analysis.

In the 24 subjects without neoadjuvant treatment, it was found that MRS-tm is able to discriminate healthy and neoplastic tissue and can discriminate patients with risk of recurrence/progression

Our data seem to show that 1H MRS may be successfully applied in vivo non-invasively to differentiate tumours from healthy mucosa and could also distinguish patients with different prognoses.

Esophageal carcinoma (EC) is one of the most common malignant tumors. EC survival has remained disappointingly low because of the high malignancy of esophageal cancer and the lack of obvious clinical symptoms at an early stage. Early diagnosis is often difficult because the small tumor nodules are frequently missed. Metabonomics based on high-resolution magic-angle spinning (HRMAS) NMR has been popular for tumor detection because it is highly sensitive, provides rich biochemical information and requires no sample pretreatment. (1)H HRMAS spectra of non-involved adjacent esophageal tissues and of well differentiated and moderately differentiated esophageal carcinoma tumors were recorded and analyzed by use of multivariate and statistical analysis techniques. Moderately differentiated EC tumors were found to have increased total choline, alanine, and glutamate and reduced creatine, myo-inositol, and taurine compared with non-involved adjacent tissues. Moreover, clear differences between the metabonomic profiles of EC tissues enabled tumor differentiation. Furthermore, the integral Gly/MI ratio for samples of different tissue types were statistically significantly different; this was sufficient both for distinguishing non-involved tissues from esophageal carcinoma and for classification of well differentiated and moderately differentiated EC tumors.