Combined pre-treatment MRI and 18F-FDG PET/CT parameters as prognostic biomarkers in patients with cervical cancer

Objective

To determine the associations of quantitative parameters derived from multiphase contrast-enhanced magnetic resonance imaging (CE-MRI), diffusion-weighted (DW) MRI and 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT) with clinico-histopathological prognostic factors, disease-free survival (DFS) and overall survival (OS) in patients with cervical cancer.

Methods and materials

Our institutional review board approved this retrospective study of 49 patients (median age, 45 years) with histopathologically proven IB-IVB International Federation of Gynecology and Obstetrics (FIGO) cervical cancer who underwent pre-treatment pelvic MRI and whole-body 18F-FDG PET/CT between February 2009 and May 2012. Maximum diameter (_maxTD), percentage enhancement (PE) and mean apparent diffusion coefficient (ADC_mean) of the primary tumor were measured on MRI. Maximum standardized uptake value (SUV_max), metabolic tumor volume (MTV), total lesion glycolysis (TLG) were measured on 18F-FDG PET/CT. Correlations between imaging metrics and clinico-histopathological parameters including revised 2009 FIGO stage, tumor histology, grade and lymph node (LN) metastasis at diagnosis were evaluated using the Wilcoxon rank sum test. Cox modeling was used to determine associations with DFS and OS.

Results

Median follow-up was 17 months. 41 patients (83.6%) were alive. 8 patients (16.3%) died of disease. Progression/recurrence occurred in 17 patients (34.6%). Significant differences were observed in ADC_mean, SUV_max, MTV and TLG according to FIGO stage (p < 0.001–0.025). There were significant correlations between ADC_mean, MTV, TLG and LN metastasis (p = 0.017–0.032). SUV_max was not associated with LN metastasis. FIGO stage (p = 0.017/0.033), LN metastases (p = 0.001/0.020), ADC_mean (p = 0.007/0.020) and MTV (p = 0.014/0.026) were adverse predictors of both DFS/OS. _maxTD (p = 0.005) and TLG (p = 0.024) were adverse predictors of DFS. PE and SUV_max did not correlate with DFS or OS (p = 0.18–0.72).

Conclusions

Quantitative parameters derived from pre-treatment DW-MRI (ADC_mean) and from 18F-FDG PET/CT (MTV and TLG) were associated with high-risk features and may serve as prognostic biomarkers of survival in patients with cervical cancer.     

Application of diffusion-weighted MR imaging with ADC measurement for distinguishing between the histopathological types of sinonasal neoplasms

PurposeTo evaluate the potential contribution of quantitative DWI parameters including ADC_mean and ADC_ratio values to help in distinguishing the histopathological types of sinonasal neoplasms.MethodsThis retrospective study included 83 patients (50 males, 33 females; mean age 61 years) with pathologically proven untreated sinonasal neoplasms who have undergone diffusion-weighted MRI imaging from February 2010 to August 2017. Diffusion-weighted MRI was performed on a 3 T unit with b factors of 0 and 1000 s/mm², and ADC maps were generated. Mean ADC values of sinonasal tumors and ADC ratios (ADC_mean of the tumor to ADC_mean of pterygoid muscles) were compared with the histopathological diagnosis by utilizing the Kruskal-Wallis non-parametric test.ResultsMean ADC_mean and ADC_ratio were 0.8 (SD, ±0.4) × (10⁻³ mm²/s) and 1.2 (SD, ±0.5), respectively, and each parameter was significantly different between histopathological types (p < 0.05). Mean ADC_mean and ADC_ratio were higher in adenoid cystic carcinoma (ACC) than in SCC, lymphoma, neuroendocrine carcinoma and sinonasal undifferentiated carcinoma (SNUC) (p < 0.05). Optimized ADC_mean thresholds of 0.79, 0.81, 0.74 and 0.78 (10⁻³ mm²/s) achieved maximal discriminatory accuracies of 100%, 79%, 100% and 89% for ACC/SNUC, ACC/SCC, ACC/neuroendocrine carcinoma, and ACC/lymphoma, respectively.ConclusionsThe optimized ADC_mean threshold of 0.80 (10⁻³ mm²/s) could be used to differentiate ACC from non-ACC sinonasal neoplasms with maximal discriminatory accuracy (82%) and sensitivity of 100%. However, there is considerable overlapping of the ADC_mean and ADC_ratio values among non-ACC sinonasal neoplasms hence surgical biopsy is still needed.     

Functional imaging of head and neck squamous cell carcinoma with diffusion-weighted MRI and FDG PET/CT: quantitative analysis of ADC and SUV

Purpose

Head and neck squamous cell carcinoma (HNSCC) may cause a decreased apparent diffusion coefficient (ADC) on diffusion-weighted magnetic resonance imaging (DW MRI) and an increased standardized uptake value (SUV) on fluorodeoxyglucose (FDG) positron emission tomography (PET/CT). We analysed the reproducibility of ADC and SUV measurements in HNSCC and evaluated whether these biomarkers are correlated or independent.

Methods

This retrospective analysis of DW MRI and FDG PET/CT data series included 34 HNSCC in 33 consecutive patients. Two experienced readers measured tumour ADC and SUV values independently. Statistical comparison and correlation with histopathology was done. Intra- and inter-observer agreement for ADC and SUV measurements was assessed.

Results

Intraclass correlation coefficient (ICC) analysis showed almost perfect reproducibility (>0.90) for ADC_mean, ADC_min, SUV_max and SUV_mean values for intra-observer and inter-observer agreement. Mean ADC_mean and ADC_min in HNSCC were 1.05?±?0.34 × 10^?3?mm²/s and 0.65?±?0.29 × 10^?3?mm²/s, respectively. Mean SUV_mean and mean SUV_max were 7.61?±?3.87 and 12.8?±?5.0, respectively. Although statistically not significant, a trend towards higher SUV and lower ADC was observed with increasing tumour dedifferentiation. Pearson’s correlation analysis showed no significant correlation between ADC and SUV measurements (r ?0.103, ?0.051; p 0.552, 0.777).

Conclusion

Our data suggest that ADC and SUV values are reproducible and independent biomarkers in HNSCC.     

Choroid Plexus as the Best Reference Region for Standardized Uptake Value Analysis on C11-Acetate PET/CT for Grading and Predicting Prognosis in Patients with Cerebral Gliomas

PurposeWe aimed to compare different reference regions and select one with the most clinical relevance on C11-acetate (ACE) positron emission tomography/computed tomography (PET/CT) in patients with cerebral glioma.MethodsWe retrospectively reviewed 51 patients with cerebral glioma who underwent baseline ACE PET/CT at diagnosis. Other than the standardized uptake value (SUV) of the primary tumor, SUVs of the reference regions including the normal gray matter, white matter, choroid plexus, and cerebellum were measured. Then, the SUV ratio (SUV_R = tumor SUV_max/reference region SUV_mean) was calculated. The effect of patient age on the SUV_mean of each reference was examined and the SUV_Rs of each reference region were compared between grades. age, sex, tumor size, histological grades, SUV_R, and the presence of isocitrate dehydrogenase (IDH) mutation were included for survival analyses.ResultsExcept for the cerebellum showing a mild negative correlation, we found no correlations between age and SUV_mean using the gray matter, white matter, and choroid plexus (r = − 0.280, P = 0.047). Only the SUV_R-choroid plexus was able to differentiate between the WHO grades (Grade II vs. III, P = 0.035; grade III vs. IV, P < 0.001; grade II vs. IV, P < 0.001). Multivariate Cox proportional hazards models found that the SUVR-choroid plexus and IDH mutation were statistically significant for predicting OS.ConclusionOf the different reference regions used for grading cerebral gliomas, the choroid plexus was found to be the most optimal. In addition, the SUV ratio is useful to predict the overall survival in the model with the choroid plexus as a reference region.     

Prognostic value of FDG-PET and DWI in breast cancer

Objective

To investigate the prognostic value of preoperative FDG-PET/CT and diffusion weighted imaging (DWI) in patients with breast cancer.

Methods

A total of 73 patients with newly diagnosed invasive breast cancer who had undergone preoperative whole-body FDG-PET/CT and 3-Tesla breast MRI including DWI followed by surgery were identified. Effects of primary tumor PET parameters [maximum standardized uptake value (SUV_max), mean SUV (SUV_mean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] and DWI parameters [mean apparent diffusion coefficient (ADC_mean) and minimum ADC (ADC_min)] including clinicopathologic factors on disease-free survival (DFS) were retrospectively evaluated using the log-rank and Cox methods.

Results

After a median overall follow-up of 32.3 months in all patients, 6 (8.2%) of the 73 patients had recurrence. Receiver operating characteristic curve analysis and log-rank tests showed that patients with a high primary tumor SUV_max (≥?3.60), MTV (≥?3.15), and TLG (≥?16.0) had a significantly lower DFS rate than those with a low SUV_max (<?3.60), MTV (<?3.15), and TLG (<?16.0), respectively (p?=?0.0054, p?=?0.0054, and p?<?0.0001, respectively). SUV_mean, ADC_mean, and ADC_min were not significantly associated with recurrence. Univariate analysis showed that SUV_max (p?=?0.0054), MTV (p?=?0.0054), TLG (p?<?0.0001), tumor size (p?=?0.0083), estrogen receptor negativity (p?=?0.046), progesterone receptor negativity (p?=?0.0023), human epidermal growth factor receptor 2 positivity (p?=?0.043), and the presence of axillary lymph node metastasis (p?=?0.0037) were also significantly associated with recurrence. However, in multivariate analysis, none of them were an independent factor.

Conclusions

The preoperative SUV_max, MTV, and TLG of primary breast cancer are prognostic factors for recurrence, whereas ADC values are not.

     

Prognostic Value of Metabolic Tumor Volume Measured by 18F-FDG PET/CT in Locally Advanced Head and Neck Squamous Cell Carcinomas Treated by Surgery

Purpose

We assessed the prognostic value of metabolic tumor volume (MTV) measured using¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) inpatients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Methods

We retrospectively reviewed 56 patients (51 men, five women; mean age 56.0 ± 8.8years) who had locally advanced HNSCC and underwent FDG PET/CT for initial evaluation. All patients had surgical resection and radiotherapy with or without concurrent chemotherapy. The peak standardized uptake value (SUV_peak) and MTV of the target lesion, including primary HNSCC andmetastatic cervical lymph nodes, were measured from FDG PET/CT images. We compared SUV_peak, MTV, and clinicopathologic variables such as age, Eastern Cooperative Oncology Group (ECOG) performance status, pN stage, pT stage, TNM stage, histologic grade and treatment modality to disease-free survival (DFS) and overall survival (OS).

Results

On the initial FDG PET/CT scans, the median SUV_peak was 7.8 (range, 1.8-19.0) and MTV was17.0 cm³ (range, 0.1-131.0 cm³). The estimated 2-year DFS and OS rates were 67.2% and 81.8%. The cutoff points of SUV_peak 6.2 and MTV 20.7 cm³ were the best discriminative values for predicting clinical outcome. MTV and ECOG performance status were significantly related to DFS and OS on univariate and multivariate analyses (p < 0.05).

Conclusion

The MTV obtained from initial FDG PET/CT scan is a significant prognostic factor for disease recurrence and mortality in locally advanced HNSCC treated with surgery and radiotherapy with or without chemotherapy.     

The value of intratumoral heterogeneity of 18F-FDG uptake to differentiate between primary benign and malignant musculoskeletal tumours on PET/CT

Objective:

The cumulative standardized uptake value (SUV)–volume histogram (CSH) was reported to be a novel way to characterize heterogeneity in intratumoral tracer uptake. This study investigated the value of fluorine-18 fludeoxyglucose (¹⁸F-FDG) intratumoral heterogeneity in comparison with SUV to discriminate between primary benign and malignant musculoskeletal (MS) tumours.

Methods:

The subjects comprised 85 pathologically proven MS tumours. The area under the curve of CSH (AUC-CSH) was used as a heterogeneity index, with lower values corresponding with increased heterogeneity. As 22 tumours were indiscernible on ¹⁸F-FDG positron emission tomography, maximum standardized uptake value (SUV_max), mean standardized uptake value (SUV_mean) and AUC-CSH were obtained in 63 positive tumours. The Mann–Whitney U test and receiver operating characteristic (ROC) analysis were used for analyses.

Results:

The difference between benign (n = 35) and malignant tumours (n = 28) was significant in AUC-CSH (p = 0.004), but not in SUV_max (p = 0.168) and SUV_mean (p = 0.879). The sensitivity, specificity and accuracy for diagnosing malignancy were 61%, 66% and 64% for SUV_max (optical threshold value, >6.9), 54%, 60% and 57% for SUV_mean (optical threshold value, >3) and 61%, 86% and 75% for AUC-CSH (optical threshold value, ≤0.42), respectively. The area under the ROC curve was significantly higher in AUC-CSH (0.71) than SUV_max (0.60) (p = 0.018) and SUV_mean (0.51) (p = 0.005).

Conclusion:

The heterogeneity index, AUC-CSH, has a higher diagnostic accuracy than SUV analysis in differentiating between primary benign and malignant MS tumours, although it is not sufficiently high enough to obviate histological analysis.

Advances in knowledge:

AUC-CSH can assess the heterogeneity of ¹⁸F-FDG uptake in primary benign and malignant MS tumours, with significantly greater heterogeneity associated with malignant MS tumours. AUC-CSH is more diagnostically accurate than SUV analysis in differentiating between benign and malignant MS tumours.     

Chemoradiation-induced changes in systemic inflammatory markers and their prognostic significance in oesophageal squamous cell carcinoma

Objective:Chemoradiation (CRT) may induce a change in systemic inflammatory state which could affect clinical outcomes in oesophageal cancer. We aimed to evaluate the changes and prognostic significance of systemic inflammatory markers following definitive CRT in oesophageal squamous cell carcinoma.Methods:A total of 53 patients treated with concurrent CRT were included in this retrospective analysis. We compared neutrophils, lymphocytes, platelets, neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) before and after CRT using Wilcoxon signed-rank test. Overall survival (OS) and progression-free survival (PFS) were calculated. Univariable and multivariable survival analysis were performed using Cox regression analysis. Clinical univariable survival prognostic factors with p < 0.1 were included in a multivariable cox regression analysis for backward stepwise model selection.Results:Both NLR (median ∆+2.8 [IQR −0.11, 8.62], p < 001) and PLR (median ∆+227 [81.3–523.5], p < 0.001) increased significantly after CRT. Higher levels of pre-CRT, post-CRT and change (∆) in NLR and PLR were associated with inferior OS and PFS. Post-CRT NLR (HR 1.04, 95% CI 1.02–1.07, p < 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.005), cT-stage (HR 3.83, 95% CI 1.39–10.60, p = 0.01) and RT dose (HR 0.41, 95% CI 0.21–0.81, p = 0.01) were independent prognostic factors for OS in multivariable analysis. Change in NLR (HR 1.04, 95% CI 1.01–1.06, p = 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.002), cT-stage (HR 3.98, 95% CI 1.55–10.25, p = 0.004) and RT dose (HR 0.41, 95% CI 0.21–0.80, p = 0.009) were independent prognostic factors for PFS.Conclusion:Both NLR and PLR increased following definitive CRT. Post-CRT NLR and ∆NLR were associated with adverse survival in oesophageal SCC.Advances in knowledge:We showed that CRT increased PLR and NLR, possibly reflecting a systemic inflammatory state which were associated with poor clinical outcomes in oesophageal SCC.     

The role of pre-treatment diffusion-weighted MRI in predicting long-term outcome of colorectal liver metastasis

Objective:

To determine the prognostic value of pre-treatment apparent diffusion coefficient (ADC) of colorectal liver metastases in predicting disease response, progression-free survival (PFS) and overall survival (OS).

Methods:

We retrospectively reviewed 102 patients who underwent pre-treatment diffusion-weighted MRI using a breath-hold (b=0, 150, 500) or a free-breathing (b=0, 50, 100, 250, 500, 750) technique. The mean ADC (b=0–500) and mean flow-insensitive ADC (ADC_high) values (breath-hold: b=150 and 500; free-breathing: b=100 and 500) of up to three hepatic lesions were evaluated in each patient. Clinical and laboratory parameters were recorded. Tumour response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria at 12 weeks after treatment. Associations between tumour response, ADC values and clinical/laboratory parameters were examined by one-way analysis of variance. The relationship of ADC with PFS and OS was determined by Kaplan–Meier analysis.

Results:

62 patients responded to chemotherapy at 12 weeks. The pre-treatment mean ADC and mean ADC_high were higher in the non-responding group than in the responding group (1.55 vs 1.36, p=0.033; 1.40 vs 1.16, p=0.024). However, the PFS and OS of the two groups of patients stratified by the median of mean ADC values or threshold derived by receiver operating characteristic analysis were not statistically significant. By multivariate Cox regression analysis, patients with ≤2 metastases and response to chemotherapy showed better PFS; white cell count ≤10 and surgical treatment were associated with better OS.

Conclusion:

Colorectal liver metastasis with higher pre-treatment mean ADC and mean ADC_high was associated with poorer response to chemotherapy. However, ADC and ADC_high values did not predict the patient outcome in this study cohort.

Advances in knowledge:

High mean ADC values of colorectal liver metastases on pre-treatment diffusion-weighted MRI is associated with poorer response to chemotherapy.Liver metastasis from colorectal cancer is common and is associated with poor survival. It has been shown that liver metastectomy [1], radiofrequency ablation [2] and good response to chemotherapy confer a favourable long-term outcome [3]. Given the impact of adverse effects of current treatments on quality of life, knowledge on the likelihood to respond to chemotherapy, progression-free survival (PFS) and overall survival (OS) will also facilitate clinical decision making on how aggressively to pursue the various therapeutic options.There are several pre-treatment clinical factors that have been shown to affect the outcome in metastatic colorectal cancer [4]. Negative clinical predictors of outcome include platelets (plt) >400×10⁹ l⁻¹, alkaline phosphatase (ALP) >300 units per litre, white blood cell count (WCC) >10×10⁹ l⁻¹, and haemoglobin (Hb) <11×10⁹ l⁻¹. The presence of lung or lymph node metastases and the primary site being at the rectum are associated with better outlook. However, there is currently no imaging-derived prognostic index that is linked to treatment outcomes. An MRI prognostic feature is attractive because it can be derived non-invasively and may also be applied for response monitoring.The apparent diffusion coefficient (ADC), derived from diffusion-weighted MRI (DW-MRI), provides information on the microscopic movement of water molecules [5–7]. In neoplasms, ADC informs on cell membrane integrity, cellular density, extracellular space tortuosity and microstructural organisation [8,9]. Solid tumours usually return lower ADC values than their tissue of origin. In brain tumours, a pre-treatment ADC value has been shown to predict tumour response [10] and disease survival [11]. Although studies have shown that a high pre-treatment ADC value of colorectal liver metastases predicts poor response to chemotherapy [12,13], the relationship of pre-treatment ADC value and the patient clinical outcome has not been examined in abdominal malignancies.The aim of this study was to determine whether pre-treatment ADC of colorectal liver metastases is of prognostic value in predicting the patient outcome in terms of disease response, PFS and OS.     

MRI-defined high-risk rectal cancer patients: outcome comparison between neoadjuvant chemoradiotherapy plus TME and TME plus adjuvant chemotherapy or TME alone

Objective:The goal of this study was to investigate whether neoadjuvant chemoradiotherapy (NCRT) plus total mesorectal excision (TME) would improve the outcome of patients with MRI-defined high-risk rectal cancer compared with TME plus adjuvant chemotherapy (ACT) or TME alone.Methods:We retrospectively enrolled 362 patients with MRI-defined high-risk rectal cancer who were treated with NCRT plus TME, TME plus ACT, or TME alone between January 2008 and August 2018. Cases with a high-risk tumor stage, positive extramural venous invasion, or mesorectal fascia involvement on baseline MRI were considered cases of high-risk rectal cancer. We matched patients treated with NCRT plus TME to patients treated with TME plus ACT and to those treated with TME alone. Kaplan–Meier curves were used to compare local recurrence (LR), disease-free survival (DFS), and overall survival (OS) rates.Results:The cumulative 3 year LR rate in the matched NCRT plus TME group was more favorable than in the TME plus ACT group (0% vs 5.1%; p = 0.037; n = 98) and in the TME alone group (0% vs 11.5%; p = 0.016; n = 61). Patients who received NCRT plus TME demonstrated better cumulative 3 year DFS rates than patients treated with TME plus ACT (85.7% vs 65.3%; p = 0.009) or with TME alone (86.9% vs 68.9%; p = 0.046). No difference in OS was observed among the groups.Conclusion:NCRT may improve DFS and LR rates in patients with MRI-defined high-risk rectal cancer when compared with TME plus ACT or TME alone.Advances in knowledge:This study illustrated the specific benefit of NCRT on the outcome measures of MRI-defined high-risk rectal cancer compared with TME plus ACT or TME alone, which was not clearly clarified in previous studies enrolling all patients with Stage II/III rectal cancer.     

How to Combine Diffusion-Weighted and T2-Weighted Imaging for MRI Assessment of Pathologic Complete Response to Neoadjuvant Chemoradiotherapy in Patients with Rectal Cancer?

ObjectiveAdequate methods of combining T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) to assess complete response (CR) to chemoradiotherapy (CRT) for rectal cancer are obscure. We aimed to determine an algorithm for combining T2WI and DWI to optimally suggest CR on MRI using visual assessment.Materials and MethodsWe included 376 patients (male:female, 256:120; mean age ± standard deviation, 59.7 ± 11.1 years) who had undergone long-course CRT for rectal cancer and both pre- and post-CRT high-resolution rectal MRI during 2017–2018. Two experienced radiologists independently evaluated whether a tumor signal was absent, representing CR, on both post-CRT T2WI and DWI, and whether the pre-treatment DWI showed homogeneous hyperintensity throughout the lesion. Algorithms for combining T2WI and DWI were as follows: ‘AND,’ if both showed CR; ‘OR,’ if any one showed CR; and ‘conditional OR,’ if T2WI showed CR or DWI showed CR after the pre-treatment DWI showed homogeneous hyperintensity. Their efficacies for diagnosing pathologic CR (pCR) were determined in comparison with T2WI alone.ResultsSixty-nine patients (18.4%) had pCR. AND had a lower sensitivity without statistical significance (vs. 62.3% [43/69]; 59.4% [41/69], p = 0.500) and a significantly higher specificity (vs. 87.0% [267/307]; 90.2% [277/307], p = 0.002) than those of T2WI. Both OR and conditional OR combinations resulted in a large increase in sensitivity (vs. 62.3% [43/69]; 81.2% [56/69], p < 0.001; and 73.9% [51/69], p = 0.008, respectively) and a large decrease in specificity (vs. 87.0% [267/307]; 57.0% [175/307], p < 0.001; and 69.1% [212/307], p < 0.001, respectively) as compared with T2WI, ultimately creating additional false interpretations of CR more frequently than additional identification of patients with pCR.ConclusionAND combination of T2WI and DWI is an appropriate strategy for suggesting CR using visual assessment of MRI after CRT for rectal cancer.     

Diffusion-weighted magnetic resonance imaging for assessment of lung lesions: repeatability of the apparent diffusion coefficient measurement

Purpose

To establish repeatability of apparent diffusion coefficients (ADCs) acquired from free-breathing diffusion-weighted magnetic resonance imaging (DW-MRI) in malignant lung lesions and investigate effects of lesion size, location and respiratory motion.

Methods

Thirty-six malignant lung lesions (eight patients) were examined twice (1- to 5-h interval) using T1-weighted, T2-weighted and axial single-shot echo-planar DW-MRI (b?=?100, 500, 800 s/mm²) during free-breathing. Regions of interest around target lesions on computed b?=?800 s/mm² images by two independent observers yielded ADC values from maps (pixel-by-pixel fitting using all b values and a mono-exponential decay model). Intra- and inter-observer repeatability was assessed per lesion, per patient and by lesion size (> or <2 cm) or location.

Results

ADCs were similar between observers (mean ± SD, 1.15?±?0.28?×?10^-3 mm²/s, observer 1; 1.15?±?0.29?×?10^-3 mm²/s, observer 2). Intra-observer coefficients of variation of the mean [median] ADC per lesion and per patient were 11 % [11.4 %], 5.7 % [5.7 %] for observer 1 and 9.2 % [9.5 %], 3.9 % [4.7 %] for observer 2 respectively; inter-observer values were 8.9 % [9.3 %] (per lesion) and 3.0 % [3.7 %] (per patient). Inter-observer coefficient of variation (CoV) was greater for lesions <2 cm (n?=?20) compared with >2 cm (n?=?16) (10.8 % vs 6.5 % ADC_mean, 11.3 % vs 6.7 % ADC_median) and for mid (n?=?14) vs apical (n?=?9) or lower zone (n?=?13) lesions (13.9 %, 2.7 %, 3.8 % respectively ADC_mean; 14.2 %, 2.8 %, 4.7 % respectively ADC_median).

Conclusion

Free-breathing DW-MRI of whole lung achieves good intra- and inter-observer repeatability of ADC measurements in malignant lung tumours.

Key Points

? Diffusion-weighted MRI of the lung can be satisfactorily acquired during free-breathing ? DW-MRI demonstrates high contrast between primary and metastatic lesions and normal lung ? Apparent diffusion coefficient (ADC) measurements in lung tumours are repeatable and reliable ? ADC offers potential in assessing response in lung metastases in clinical trials     

Diffusion weighted MRI and 18F-FDG PET/CT in non-small cell lung cancer (NSCLC): Does the apparent diffusion coefficient (ADC) correlate with tracer uptake (SUV)?

Introduction

To investigate the potential correlation of the apparent diffusion coefficient assessed by diffusion-weighted MRI (DWI) and glucose metabolism determined by the standardized uptake value (SUV) at 18F-FDG PET/CT in non-small cell lung cancer (NSCLC).

Materials and methods

18F-FDG PET/CT and DWI (TR/TE, 2000/66 ms; b-values, 0 and 500 s/mm²) were performed in 41 consecutive patients with histologically verified NSCLC. Analysing the PET-CT data calculation of the mean (SUV_mean) and maximum (SUV_max) SUV was performed. By placing a region-of-interest (ROI) encovering the entire tumor mean (ADC_mean) and minimum ADC (ADC_min) were determined by two independent radiologists. Results of 18F-FDG PET-CT and DWI were compared on a per-patient basis. For statistical analysis Pearson's correlation coefficient, Bland–Altman and regression analysis were assessed.

Results

Data analysis revealed a significant inverse correlation of the ADC_min and SUV_max (r = −0.46; p = 0.032). Testing the correlation of the ADC_min and SUV_max for each histological subtype separately revealed that the inverse correlation was good for both adenocarcinomas (r = −0.47; p = 0.03) and squamouscell carcinomas (r = −0.71; p = 0.002), respectively. No significant correlation was found for the comparison of ADC_min and SUV_mean (r = −0.29; p = 0.27), ADC_mean vs. SUV_mean (r = −0.28; p = 0.31) or ADC_mean vs. SUV_max (r = −0.33; p = 0.23). The κ-value of 0.88 indicated a good agreement between both observers.

Conclusion

This preliminary study is the first to verify the relation between the SUV and the ADC in NSCLC. The significant inverse correlation of these two quantitative imaging approaches points out the association of metabolic activity and tumor cellularity. Therefore, DWI with ADC measurement might represent a new prognostic marker in NSCLC.     

Diffusion-weighted MR imaging including bi-exponential fitting for the detection of recurrent or residual tumour after (chemo)radiotherapy for laryngeal and hypopharyngeal cancers

Objectives

To assess whether diffusion-weighted magnetic resonance imaging (DW-MRI) including bi-exponential fitting helps to detect residual/recurrent tumours after (chemo)radiotherapy of laryngeal and hypopharyngeal carcinoma.

Methods

Forty-six patients with newly-developed/worsening symptoms after (chemo)radiotherapy for laryngeal/hypopharyngeal cancers were prospectively imaged using conventional MRI and axial DW-MRI. Qualitative (visual assessment) and quantitative analysis (mono-exponentially: total apparent diffusion coefficient [ADC_T], and bi-exponentially: perfusion fraction [F_P] and true diffusion coefficient [ADC_D]) were performed. Diffusion parameters of tumour versus post-therapeutic changes were compared, with final diagnosis based on histopathology and follow-up. Mann-Whitney U test was used for statistical analysis.

Results

Qualitative DW-MRI combined with morphological images allowed the detection of tumour with a sensitivity of 94% and specificity 100%. ADC_T and ADC_D values were lower in tumour with values 120 ± 49 × 10⁻⁵ mm²/s and 113 ± 50 × 10⁻⁵ mm²/s, respectively, compared with post-therapeutic changes with values 182 ± 41 × 10⁻⁵ mm²/s (P < 0.0002) and 160 ± 47 × 10⁻⁵ mm²/s (P < 0.003), respectively. F_P values were significantly lower in tumours than in non-tumours (13 ± 9% versus 31 ± 16%, P < 0.0002), with F_P being the best quantitative parameter for differentiation between post-therapeutic changes and recurrence.

Conclusions

DW-MRI in combination with conventional MRI substantially improves detection and exclusion of tumour in patients with laryngeal and hypopharyngeal cancers after treatment with (chemo)radiotherapy on both qualitative and quantitative analysis, with F_P being the best quantitative parameter in this context.

Key Points

• DW-MRI is increasingly used to detect tumour recurrence.

• DW-MRI allows accurate post-treatment recurrence detection in laryngeal or hypopharyngeal cancer

• ADC values in recurrent tumour are lower than in benign tissue alterations

• Both qualitative and quantitative DW-MRI approaches allow detection of recurrence

• DW-MRI can easily be added to daily clinical routine imaging

     

Combination of diffusion-weighted imaging and arterial spin labeling at 3.0 T for the clinical staging of nasopharyngeal carcinoma

PurposeTo probe the utility of diffusion-weighted imaging (DWI) and 3D arterial spin labeling (ASL) in assessing the clinical stage of nasopharyngeal carcinoma (NPC).Materials and methodsThis prospective study included sixty-five newly diagnosed NPC patients who underwent DWI and 3D ASL scans on a 3.0-T magnetic resonance imaging (MRI) system. The apparent diffusion coefficient (ADC) and the tumor blood flow (TBF) of NPC were measured. Tumors were classified as low or high T, N and American Joint Committee on Cancer (AJCC) stages. Student's t-test was used to evaluate the differences between tumors with low and high clinical stages. Pearson correlation analyses were performed to determine the correlation between MRI parameters and clinical stages. Receiver operating characteristic (ROC) curves were then used to evaluate diagnostic capability.ResultsHigh T stage (T3/4) NPC showed significantly lower ADC_min (P = 0.000) and higher TBF_max (P = 0.003) and TBF_mean (P = 0.008) values than low T stage (T1/2) NPC. High N stage (N2/3) NPC showed significantly lower ADC_min values (P = 0.023) than low N stage (N0/1) NPC. High AJCC stage (III/IV) NPC showed significantly lower ADC_min (P = 0.000) and higher TBF_max (P = 0.005) and TBF_mean (P = 0.011) values than low AJCC stage (I/II) NPC. ADC_min values showed moderate negative correlations with T stage (r = −0.512, P = 0.000), N stage (r = −0.281, P = 0.023), and AJCC stage (r = −0.494, P = 0.000). TBF_max values showed moderate positive correlations with T stage (r = 0.369, P = 0.003) and AJCC stage (r = 0.346, P = 0.005). Compared with ADC_min and TBF_max alone, the combination of ADC_min and TBF_max improved the accuracy from 72.3% and 75.4% to 78.5%, respectively, for T staging, as well as from 72.3% and 69.2% to 83.1% for AJCC staging.ConclusionsADC_min and TBF_max values in patients with NPC could help evaluate clinical stages. ADC_min and TBF_max values combined could clearly improve the accuracy in the assessment of AJCC stage.     

T1 mapping for the diagnosis of early chronic pancreatitis: correlation with Cambridge classification system

Objective:This study aims to determine if T1 relaxation time of the pancreas can detect parenchymal changes in early chronic pancreatitis (CP).Methods:This study retrospectively analyzed 42 patients grouped as no CP (Cambridge 0; n = 21), equivocal (Cambridge 1; n = 12) or mild CP (Cambridge 2; n = 9) based on magnetic resonance cholangiopancreatography findings using the Cambridge classification as the reference standard. Unenhanced T1 maps were acquired using a three-dimensional dual flip-angle gradient-echo technique on the same 1.5 T scanner with the same imaging parameters.Results:There was no significant difference between the T1 relaxation times of Cambridge 0 and 1 group (p = 0.58). There was a significant difference (p = 0.0003) in the mean T1 relaxation times of the pancreas between the combined Cambridge 0 and 1 (mean = 639 msec, 95% CI: 617, 660) and Cambridge 2 groups (mean = 726 msec, 95% CI: 692, 759). There was significant difference (p = 0.0009) in the mean T1 relaxation times of the pancreas between the Cambridge 0 (mean = 636 msec, 95% CI: 606, 666) and Cambridge 2 groups (mean = 726 msec, 95% CI: 692,759) as well as between Cambridge 1 (mean = 643 msec, 95% CI: 608, 679) and Cambridge 2 groups (mean = 726 msec, 95% CI: 692,759) (p = 0.0017). Bland–Altman analysis showed measurements of one reader to be marginally higher than the other by 15.7 msec (2.4%, p = 0.04).Conclusion:T1 mapping is a practical method capable of quantitatively reflecting morphologic changes even in the early stages of chronic pancreatitis, and demonstrates promise for future implementation in routine clinical imaging protocols.Advances in knowledge:T1 mapping can distinguish subtle parenchymal changes seen in early stage CP, and demonstrates promise for implementation in routine imaging protocols for the diagnosis of CP.     

Changes in dynamic contrast-enhanced pharmacokinetic and diffusion-weighted imaging parameters reflect response to anti-TNF therapy in Crohn's disease

Objective:

To investigate the effect of tumour necrosis factor (TNF)-α antagonists on MRI dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI) parameters in Crohn''s disease (CD).

Methods:

42 patients with CD (median age 24 years; 22 females) commencing anti-TNF-α therapy with baseline and follow-up (median 51 weeks) 1.5-T MR enterography (MRE) were retrospectively identified. MRE included DCE (n = 20) and/or multi-b-value DWI (n = 17). Slope of enhancement (SoE), maximum enhancement (ME), area under the time–intensity curve (AUC), K_trans (transfer constant), v_e (fractional volume of the extravascular–extracellular space), apparent diffusion coefficient (ADC) and ADC_fast/slow were derived from the most inflamed bowel segments. A physician global assessment of disease activity (remission, mild, moderate and severe) at the time of MRE was assigned, and the cohort was divided into responders and non-responders. Data were compared using Mann–Whitney U test and analysis of variance.

Results:

Follow-up K_trans, ME, SoE, AUC and ADC_ME changed significantly in clinical responders but not in non-responders, baseline {[median [interquartile range (IQR)]: 0.42 (0.38), 1.24 (0.52), 0.18 (0.17), 17.68 (4.70) and 1.56 mm² s⁻¹ (0.39 mm² s⁻¹) vs follow-up [median (IQR): 0.15 (0.22), 0.50 (0.54), 0.07 (0.1), 14.73 (2.06) and 2.14 mm² s⁻¹ (0.62 mm² s⁻¹), for responders, respectively, p = 0.006 to p = 0.037}. SoE was higher and ME and AUC lower for patients in remission than for those with severe activity [mean (standard deviation): 0.55 (0.46), 0.49 (0.28), 14.32 (1.32)] vs [0.32 (0.37), 2.21 (2.43) and 23.05 (13.66), respectively p = 0.017 to 0.033]. ADC was significantly higher for patients in remission [2.34 mm² s⁻¹ (0.67 mm² s⁻¹)] than for those with moderate [1.59 mm² s⁻¹ (0.26 mm² s⁻¹)] (p = 0.005) and severe disease [1.63 mm² s⁻¹ (0.21 mm² s⁻¹)] (p = 0.038).

Conclusion:

DCE and DWI parameters change significantly in responders to TNF-α antagonists and are significantly different according to clinically defined disease activity status.

Advances in knowledge:

DCE and DWI parameters change significantly in responders to TNF-α antagonists in CD, suggesting an effect on bowel wall vascularity.     

Dosimetric effect of the intestinal gas of online adaptive stereotactic body radiotherapy on target and critical organs without online electron density correction for pancreatic cancer

Objective:This study aimed to assess the dosimetric effect of intestinal gas of stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) on target and critical organs for pancreatic cancer without online electron density correction (EDC).Methods:Thirty pancreatic cancer patients who underwent online SMART were selected for this study. The treatment time of each stage and the total treatment time were recorded and analyzed. The concerned dose-volume parameters of target and organs-at-risk (OAR) were compared with and without an intestinal gas EDC using the Wilcoxon-signed rank test. Analysis items with p value < 0.05 were considered statistically significant. The relationships between dosimetric differences and intestinal gas volume variations were investigated using the Spearman test.Results:The average treatment time was 82 min, and the average EDC time was 8 min, which accounted for 10% of the overall treatment time. There were no significant differences in CTV (GTV), PTV, bowel, stomach, duodenum, and skin (p > 0.05) with respect to dose volume parameters. For the D_max of gastrointestinal organs (p = 0.03), the mean dose of the liver (p = 0.002) and kidneys (p = 0.03 and p = 0.04 for the left and right kidneys, respectively), there may be a risk of slight overestimation compared with EDC, and for the D_max of the spinal cord (p = 0.02), there may be a risk of slight underestimation compared with EDC. A weak correlation for D₉₅ in the PTV and D_{0.5 cc} in the duodenum was observed.Conclusion:For patients with similar inter-fractional intestinal gas distribution, EDC had little dosimetric effects on the D_{0.5 cc} of all GI organs and dose volume parameters of target in most plans.Advances in knowledge:By omitting the EDC of intestinal gas, the online SMART treatment time can be shortened.     

A comparison of high b-value vs standard b-value diffusion-weighted magnetic resonance imaging at 3.0?T for medulloblastomas

Objective:

To investigate the utility of diffusion-weighted (DW) MRI using high b-value vs standard b-value for patients with medulloblastoma (MB). Minimum apparent diffusion coefficient (ADC_MIN) values were also compared with tumour cellularity.

Methods:

High and standard b-value DW images were obtained for 17 patients with MB. The number and location of the lesions, signal intensities (SIs), signal-to-noise ratios (SNRs), contrast-to-noise ratios, contrast ratios (CRs) and ADCs of the lesions were compared. Tumour cellularity was also measured and compared with ADC_MIN values.

Results:

All 20 lesions were hyperintense on the DW MR images with high and standard b-values. Four additional lesions were revealed on high b-value, and all 24 lesions were more conspicuous at high b-value. SI, SNR and ADC values for the lesions were lower in the high b-value images than in the standard b-value images. The ADC_MIN value at b = 3000 s mm⁻² was more significantly associated with tumour cellularity than that at b = 1000 s mm⁻². CR values were significantly higher in the high b-value images than in the standard b-value images.

Conclusion:

DW imaging using high b-value may be beneficial for detecting additional, less prominent lesions and may improve the contrast between MB lesions and normal tissue. A stronger inverse correlation with tumour cellularity was identified using the ADC_MIN values at high b-value.

Advances in knowledge:

This study demonstrates the superiority of high b-value DW imaging compared with standard b-value imaging for the detection of MB lesions, especially those with subtle foci.     

Prognostic value of ADC measurements in predicting overall survival in patients undergoing 90Y radioembolization for colorectal cancer liver metastases

AimTo assess the ability of diffusion-weighted imaging (DWI) in predicting the overall survival in patients who underwent Yttrium 90 radioembolization (⁹⁰Y-RE) for colorectal liver metastases (CLM) with other well-established clinical and imaging parameters by comparing the pre- and post-treatment apparent diffusion coefficient (ADC) values of the lesions.MethodsA total of 81 metastatic lesions of 27 consecutive patients who underwent DWI before and after the ⁹⁰Y-RE session were enrolled in the study. ADC values were calculated from the entire (ADC_e) and peripheral (ADC_p) tumor on pre- and post-treatment DWI, and any relative increase in ADC >0% accepted as a functional imaging response. The impact of functional imaging response in addition to other well-known parameters including Response Evaluation Criteria in Solid Tumors (RECIST), hepatic tumor burden, Eastern Cooperative Oncology Group performance status (ECOG–PS) and the presence of extrahepatic metastases in predicting overall survival (OS) was assessed using Kaplan-Meier curves and Cox-regression analyses.ResultsThe median OS of the patients was 10 months (range, 6–20 months) while the median OS of the responders being significantly longer than the non-responders for ADC_e and ADC_p (median 11 vs 7 months, P = 0.003; median 12 vs. 7 months, P < 0.0001, respectively). The RECIST score was also significantly affected the OS (progressive or stable disease median 8 months vs. partial response 15 indent months, P = 0.019). The other parameters including hepatic tumor burden, gender, ECOG score, the involvement of the liver lobes, and the presence of extrahepatic metastases were not associated with the OS. In multivariate analysis, only ADC_p remained as an independent predictor of OS (P = 0.003, HR = 19.878).ConclusionAny increase in relative ADC_p or ADC_e values after Y90-RE treatment was associated with longer OS in CLM patients, and DWI seems to be valuable imaging biomarker in predicting OS in CLM patients during the early post-interventional period after ⁹⁰Y-RE.