Physiological properties of tumors can be measured both in vivo and noninvasively by diffusion‐weighted imaging and dynamic contrast‐enhanced magnetic resonance imaging. Although these techniques have been used for more than two decades to study tumor diffusion, perfusion, and/or permeability, the methods and studies on how to reduce measurement error and bias in the derived imaging metrics is still lacking in the literature. This is of paramount importance because the objective is to translate these quantitative imaging biomarkers (QIBs) into clinical trials, and ultimately in clinical practice. Standardization of the image acquisition using appropriate phantoms is the first step from a technical performance standpoint. The next step is to assess whether the imaging metrics have clinical value and meet the requirements for being a QIB as defined by the Radiological Society of North America's Quantitative Imaging Biomarkers Alliance (QIBA). The goal and mission of QIBA and the National Cancer Institute Quantitative Imaging Network (QIN) initiatives are to provide technical performance standards (QIBA profiles) and QIN tools for producing reliable QIBs for use in the clinical imaging community. Some of QIBA's development of quantitative diffusion‐weighted imaging and dynamic contrast‐enhanced QIB profiles has been hampered by the lack of literature for repeatability and reproducibility of the derived QIBs. The available research on this topic is scant and is not in sync with improvements or upgrades in MRI technology over the years. This review focuses on the need for QIBs in oncology applications and emphasizes the importance of the assessment of their reproducibility and repeatability. Level of Evidence: 5 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;49:e101–e121.

Background & Aims Consumption of sugar is associated with obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease, and cardiovascular disease. The conversion of fructose to fat in liver (de novo lipogenesis, DNL) may be a modifiable pathogenetic pathway. We determined the effect of 9 days of isocaloric fructose restriction on DNL, liver fat, visceral fat (VAT), subcutaneous fat, and insulin kinetics in obese Latino and African American children with habitual high sugar consumption (fructose intake more than 50 g/day). Methods Children (9–18 years old; n = 41) had all meals provided for 9 days with the same energy and macronutrient composition as their standard diet, but with starch substituted for sugar, yielding a final fructose content of 4% of total kcal. Metabolic assessments were performed before and after fructose restriction. Liver fat, VAT, and subcutaneous fat were determined by magnetic resonance spectroscopy and imaging. The fractional DNL area under the curve value was measured using stable isotope tracers and gas chromatography/mass spectrometry. Insulin kinetics were calculated from oral glucose tolerance tests. Paired analyses compared change from day 0 to day 10 within each child. Results Compared with baseline, on day 10, liver fat decreased from a median of 7.2% (inter-quartile range, 2.5%–14.8%) to 3.8% (inter-quartile range, 1.7%–15.5%)(P<.001) and VAT decreased from 123 cm3 (inter-quartile range, 85–145 cm3) to 110 cm3 (inter-quartile range, 84–134 cm3) (P<.001). The DNL area under the curve decreased from 68% (inter-quartile range, 46%–83%) to 26% (inter-quartile range, 16%–37%) (P<0.001). Insulin kinetics improved (P<.001). These changes occurred irrespective of baseline liver fat. Conclusions Short-term (9 day) isocaloric fructose restriction decreased liver fat, VAT, and DNL, and improved insulin kinetics in children with obesity. These findings support efforts to reduce sugar consumption. ClinicalTrials.gov no: NCT01200043

Short-term high-fructose intake was associated with increased DNL and liver fat in healthy men fed weight-maintaining diets.

Objective Dietary fructose is implicated in metabolic syndrome, but intervention studies are confounded by positive caloric balance, changes in adiposity, or artifactually high amounts. We determined whether isocaloric substitution of starch for sugar would improve metabolic parameters in Latino (n=27) and African-American (n=16) children with obesity and metabolic syndrome. Methods Participants consumed a diet for nine days to deliver comparable percentages of protein, fat, and carbohydrate as their self-reported diet; however, dietary sugar was reduced from 28% to 10%, and substituted with starch. Participants recorded daily weights, with calories adjusted for weight maintenance. Participants underwent dual-energy X-ray absorptiometry (DXA) and oral glucose tolerance testing (OGTT) on Days 0 and 10. Biochemical analyses were controlled for weight change by repeated measures ANCOVA. Results Reductions in diastolic BP (−5 mmHg; p=0.002), lactate (−0.3 mmol/L; p<0.001), triglyceride and LDL-cholesterol (−46% and −0.3 mmol/L; p<0.001) were noted. Glucose tolerance and hyperinsulinemia improved (p<0.001). Weight reduced by 0.9±0.2 kg (p<0.001) and fat-free mass by 0.6 kg (p=0.04). Post-hoc sensitivity analysis demonstrates that results in the subcohort that did not lose weight (n=10) were directionally consistent Conclusions Isocaloric fructose restriction improved surrogate metabolic parameters in children with obesity and metabolic syndrome irrespective of weight change.

A quantitative measure of three-dimensional breast density derived from noncontrast magnetic resonance imaging (MRI) was investigated in 35 women at high-risk for breast cancer. A semiautomatic segmentation tool was used to quantify the total volume of the breast and to separate volumes of fibroglandular and adipose tissue in noncontrast MRI data. The MRI density measure was defined as the ratio of breast fibroglandular volume over total volume of the breast. The overall correlation between MRI and mammographic density measures was R2=.67. However the MRI/mammography density correlation was higher in patients with lower breast density (R2=.73) than in patients with higher breast density (R2=.26). Women with mammographic density higher than 25% exhibited very different magnetic resonance density measures spread over a broad range of values. These results suggest that MRI may provide a volumetric measure more representative of breast composition than mammography, particularly in groups of women with dense breasts. Magnetic resonance imaging density could potentially be quantified and used for a better assessment of breast cancer risk in these populations.

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This study characterized dynamic contrast-enhanced (DCE) MRI of prostate tissues: cancerous peripheral zone (PZ), normal PZ, stromal benign prostatic hyperplasia (BPH), and glandular BPH. MRI, MRSI, and DCE MRI were performed on 25 patients. Tissues were identified with MRI, MRSI, and (when available) biopsy results. Motion between MRI and DCE MRI, and within DCE MRI was assessed and manually corrected. To assess tissue and patient effects, native T 1 's were measured in 12 of 25 patients, and DCE MRI results were normalized to muscle enhancement. Regions of cancer had a higher peak enhancement (P < 0.006), faster enhancement rate (P < 0.0008), and faster washout slope (P < 0.05) than normal PZ tissues. Stromal BPH had the fastest enhancement rate (P < 0.003) of all tissues and tended to have the greatest enhancement. Intersequence motion averaged 2.6 mm and reached 7.9 mm. Motion within DCE MRI was generally minimal (<2 pixels), but one case showed a large shift that would have confounded the results. Native T 1 's were similar across the prostatic tissues. Interpatient variability in DCE MRI was only partially reduced by normalization to muscle. DCE MRI of the prostate discriminated PZ cancer from normal PZ tissues and predominantly stromal and glandular BPH. Magn Reson Med 53:249 -255, 2005.

Combined MRI and 3D spectroscopic imaging (MRI/3D-MRSI) was used to study the metabolic effects of hormonedeprivation therapy in 65 prostate cancer patients, who underwent either short, intermediate, or long-term therapy, compared to 30 untreated control patients. There was a significant time-dependent loss of the prostatic metabolites choline, creatine, citrate, and polyamines during hormonedeprivation therapy, resulting in the complete loss of all observable metabolites (total metabolic atrophy) in 25% of patients on long-term therapy. The amount and time-course of metabolite loss during therapy significantly differed for healthy and malignant tissues. Citrate levels decreased faster than choline and creatine levels during therapy, resulting in an increase in the mean (choline ؉ creatine)/citrate ratio with duration of therapy. Due to a loss of all MRSI detectable citrate, this ratio could not be used to identify cancer in 69% of patients on long-term therapy. In the absence of citrate, however, residual prostate cancer could still be detected by elevated choline levels (choline/creatine ratio ≥ 1.5), or the presence of only choline in the proton spectrum.