Dynamic Contrast-Enhanced MR Imaging Predicts Local Control in Oropharyngeal or Hypopharyngeal Squamous Cell Carcinoma Treated with Chemoradiotherapy

The role of pretreatment dynamic contrast-enhanced perfusion MR imaging (DCE-PWI) and diffusion-weighted MR imaging (DWI) in predicting the treatment response of oropharyngeal or hypopharyngeal squamous cell carcinoma (OHSCC) to chemoradiation remains unclear. We prospectively investigated the ability of pharmacokinetic parameters derived from pretreatment DCE-PWI and DWI to predict the local control of OHSCC patients treated with chemoradiation. Between August, 2010 and March, 2012, patients with untreated OHSCC scheduled for chemoradiation were eligible for this prospective study. DCE-PWI and DWI were performed in addition to conventional MRI. The relationship of local control with the following clinical and imaging variables was analyzed: the hemoglobin level, T-stage, tumor location, gross tumor volume, maximum standardized uptake value, metabolic tumor volume and total lesion glycolysis on FDG PET/CT, transfer constant (K ^trans), volume of blood plasma and volume of extracellular extravascular space on DCE-PWI, and apparent diffusion coefficient on DWI of the primary tumor. The patients were also divided into a local control group and a local failure group, and their clinical and imaging parameters were compared. There were 58 patients (29 with oropharynx squamous cell carcinoma [SCC] and 29 with hypopharynx SCC) with successful pretreatment DCE-PWI and DWI available for analysis. After a median follow-up of 18.2 months, 17 (29.3%) participants had local failure, whereas the remaining 41 patients achieved local control. Univariate analysis revealed that only the K ^trans value was significantly associated with local control (P = 0.03). When the local control and local failure groups were compared, significant differences were observed in K ^trans and the tumor location (P = 0.01 and P = 0.04, respectively). In the multivariable analysis, only K ^trans was statistically significant (P = 0.04). Our results suggest that pretreatment K ^trans may help predict the local control in OHSCC patients treated with chemoradiation.     

18F-FDG PET Metabolic Parameters and MRI Perfusion and Diffusion Parameters in Hepatocellular Carcinoma: A Preliminary Study

Objectives

Glucose metabolism, perfusion, and water diffusion may have a relationship or affect each other in the same tumor. The understanding of their relationship could expand the knowledge of tumor characteristics and contribute to the field of oncologic imaging. The purpose of this study was to evaluate the relationships between metabolism, vasculature and cellularity of advanced hepatocellular carcinoma (HCC), using multimodality imaging such as ¹⁸F-FDG positron emission tomography (PET), dynamic contrast enhanced (DCE)-MRI, and diffusion weighted imaging(DWI).

Materials and Methods

Twenty-one patients with advanced HCC underwent ¹⁸F-FDG PET, DCE-MRI, and DWI before treatment. Maximum standard uptake values (SUV_max) from ¹⁸F-FDG-PET, variables of the volume transfer constant (K^trans) from DCE-MRI and apparent diffusion coefficient (ADC) from DWI were obtained for the tumor and their relationships were examined by Spearman’s correlation analysis. The influence of portal vein thrombosis on SUV_max and variables of K^trans and ADC was evaluated by Mann-Whitney test.

Results

SUV_max showed significant negative correlation with K^trans _max (ρ = −0.622, p = 0.002). However, variables of ADC showed no relationship with variables of K^trans or SUV_max (p>0.05). Whether portal vein thrombosis was present or not did not influence the SUV _max and variables of ADC and K^trans (p>0.05).

Conclusion

In this study, SUV was shown to be correlated with K_trans in advanced HCCs; the higher the glucose metabolism a tumor had, the lower the perfusion it had, which might help in guiding target therapy.     

Noninvasive Assessment of Response to Neoadjuvant Chemotherapy in Osteosarcoma of Long Bones with Diffusion-Weighted Imaging: An Initial In Vivo Study

Objectives

The purpose of our study is to investigate whether diffusion-weighted imaging (DWI) is useful for monitoring the therapeutic response after neoadjuvant chemotherapy in osteosarcoma of long bones.

Materials and methods

Conventional magnetic resonance imaging (MRI) and DWI were obtained from 35 patients with histologically proven osteosarcomas. MR examinations were performed in all patients before and after 4 courses of preoperative neoadjuvant chemotherapy. Apparent diffusion coefficients (ADC) were measured. The degree of tumor necrosis was assessed macroscopically and histologically by two experienced pathologists after operation. Student’s t test was performed for testing changes in ADC value. Pearson’s correlation coefficient was used to estimate the correlation between necrosis rate and post- neoadjuvant chemotherapy ADC values. P<0.05 was considered to denote a significant difference.

Results

The difference of the whole osteosarcoma between pre- neoadjuvant chemotherapy ADC value (1.24±0.17×10⁻³ mm²/s) and post- (1.93±0.39×10⁻³ mm²/s) was significant difference (P<0.01). Regarding in patients with good response, the post- neoadjuvant chemotherapy values were significantly higher than the pre- neoadjuvant chemotherapy values (P<0.01). The post- neoadjuvant chemotherapy ADC value in patients with good response was higher than that of poor response (t = 8.995, P<0.01). The differences in post- neoadjuvant chemotherapy ADC between viable (1.03±0.17×10⁻³ mm²/s) and necrotic (2.38±0.25×10⁻³ mm²/s) tumor was highly significant (t = 23.905, P<0.01). A positive correlation between necrosis rates and the whole tumor ADC values (r = 0.769, P<0.01) was noted, but necrosis rates were not correlated with the ADC values of necrotic (r = −0.191, P = 0.272) and viable tumor areas (r = 0.292, P = 0.089).

Conclusions

DWI can identify residual viable tumor tissues and tumor necrosis induced by neoadjuvant chemotherapy in osteosarcoma. The ADC value can directly reflect the degree of tumor necrosis, and it is useful to evaluate the preoperative neoadjuvant chemotherapy response in patients with osteosarcoma.     

Radiofrequency Ablation of Liver VX2 Tumor: Experimental Results with MR Diffusion-Weighted Imaging at 3.0T

Purpose

To evaluate the value of DWI in detecting the lesions of pre- and post-radiofrequency ablation (RFA) of the rabbit liver VX2 tumors.

Materials and Methods

Twenty-two New Zealand White rabbits were tested. The protocol was approved by the Committee on the Ethics of Animal Experiments. Twenty separate tumor fragments were implanted into the livers of 20 rabbits, the liver was exposed by performing midline laparotomy. 3.0T MR DWI (b = 0, 200, 400, 600, 800,1000 s/mm²) were performed 14–21 days after tumor implantation (mean, 17 days) in the 18 tumor-bearing animals. Then RFA was performed in the 18 tumor-bearing animals and in the two healthy animals. 3.0T MR DWI was performed 7–10 days after RFA (mean, 8 days). Pathology exam was performed immediately after the completion of post- RFA MR imaging. Analyzing the features of MRI and ADC values in the pre- and post- RFA lesions of the VX2 tumors, and histopathologic results were compared with imaging findings.

Results

The difference of ADC value between viable tumor and normal liver parenchyma was significant (P<.001). After RFA, when b = 200, 400, 600, 800, 1000 s/mm², the differences of ADC values of viable tumor, granulation tissue, necrosis, normal liver parenchyma were significant (P<.001). At the time the animals were sacrificed after RFA and MR imaging, histopathologic results of local viable tumors were found in 9 (50%) of the 18 treated tumors. Macroscopic viable tumors were found at the RFA sites in 3 (17%), all 3 macroscopic viable tumors were visualized at the periphery of the RFA areas.

Conclusions

3.0T MR DWI can be used to follow up the progress of the RFA lesion, it is useful in detecting different tissues after RFA, and it is valuable in the further clinical research.     

Dynamic Contrast Enhanced MRI Detects Early Response to Adoptive NK Cellular Immunotherapy Targeting the NG2 Proteoglycan in a Rat Model of Glioblastoma

There are currently no established radiological parameters that predict response to immunotherapy. We hypothesised that multiparametric, longitudinal magnetic resonance imaging (MRI) of physiological parameters and pharmacokinetic models might detect early biological responses to immunotherapy for glioblastoma targeting NG2/CSPG4 with mAb9.2.27 combined with natural killer (NK) cells. Contrast enhanced conventional T1-weighted MRI at 7±1 and 17±2 days post-treatment failed to detect differences in tumour size between the treatment groups, whereas, follow-up scans at 3 months demonstrated diminished signal intensity and tumour volume in the surviving NK+mAb9.2.27 treated animals. Notably, interstitial volume fraction (v_e), was significantly increased in the NK+mAb9.2.27 combination therapy group compared mAb9.2.27 and NK cell monotherapy groups (p = 0.002 and p = 0.017 respectively) in cohort 1 animals treated with 1 million NK cells. v_e was reproducibly increased in the combination NK+mAb9.2.27 compared to NK cell monotherapy in cohort 2 treated with increased dose of 2 million NK cells (p<0.0001), indicating greater cell death induced by NK+mAb9.2.27 treatment. The interstitial volume fraction in the NK monotherapy group was significantly reduced compared to mAb9.2.27 monotherapy (p<0.0001) and untreated controls (p = 0.014) in the cohort 2 animals. NK cells in monotherapy were unable to kill the U87MG cells that highly expressed class I human leucocyte antigens, and diminished stress ligands for activating receptors. A significant association between apparent diffusion coefficient (ADC) of water and v_e in combination NK+mAb9.2.27 and NK monotherapy treated tumours was evident, where increased ADC corresponded to reduced v_e in both cases. Collectively, these data support histological measures at end-stage demonstrating diminished tumour cell proliferation and pronounced apoptosis in the NK+mAb9.2.27 treated tumours compared to the other groups. In conclusion, v_e was the most reliable radiological parameter for detecting response to intralesional NK cellular therapy.     

Comparison of Two Mathematical Models of Cellularity Calculation

OBJECT: Nowadays, there is increasing evidence that functional magnetic resonance imaging (MRI) modalities, namely, diffusion-weighted imaging (DWI) and dynamic-contrast enhanced MRI (DCE MRI), can characterize tumor architecture like cellularity and vascularity. Previously, two formulas based on a logistic tumor growth model were proposed to predict tumor cellularity with DWI and DCE. The purpose of this study was to proof these formulas. METHODS: 16 patients with head and neck squamous cell carcinomas were included into the study. There were 2 women and 14 men with a mean age of 57.0 ± 7.5 years. In every case, tumor cellularity was calculated using the proposed formulas by Atuegwu et al. In every case, also tumor cell count was estimated on histopathological specimens as an average cell count per 2 to 5 high-power fields. RESULTS: There was no significant correlation between the calculated cellularity and histopathologically estimated cell count by using the formula based on apparent diffusion coefficient (ADC) values. A moderate positive correlation (r=0.515, P=.041) could be identified by using the formula including ADC and V_e values. CONCLUSIONS: The formula including ADC and V_e values is more sensitive to predict tumor cellularity than the formula including ADC values only.     

Quantitative Liver MRI Combining Phase Contrast Imaging,Elastography, and DWI: Assessment of Reproducibility and Postprandial Effect at 3.0 T

Purpose

To quantify short-term reproducibility (in fasting conditions) and postprandial changes after a meal in portal vein (PV) flow parameters measured with phase contrast (PC) imaging, liver diffusion parameters measured with multiple b value diffusion-weighted imaging (DWI) and liver stiffness (LS) measured with MR elastography (MRE) in healthy volunteers and patients with liver disease at 3.0 T.

Materials and Methods

In this IRB–approved prospective study, 30 subjects (11 healthy volunteers and 19 liver disease patients; 23 males, 7 females; mean age 46.5 y) were enrolled. Imaging included 2D PC imaging, multiple b value DWI and MRE. Subjects were initially scanned twice in fasting state to assess short-term parameter reproducibility, and then scanned 20 min. after a liquid meal. PV flow/velocity, LS, liver true diffusion coefficient (D), pseudodiffusion coefficient (D*), perfusion fraction (PF) and apparent diffusion coefficient (ADC) were measured in fasting and postprandial conditions. Short-term reproducibility was assessed in fasting conditions by measuring coefficients of variation (CV) and Bland-Altman limits of agreement. Differences in MR metrics before and after caloric intake and between healthy volunteers and liver disease patients were assessed.

Results

PV flow parameters, D, ADC and LS showed good to excellent short-term reproducibility in fasting state (CV <16%), while PF and D* showed acceptable and poor reproducibility (CV = 20.4% and 51.6%, respectively). PV flow parameters and LS were significantly higher (p<0.04) in postprandial state while liver diffusion parameters showed no significant change (p>0.2). LS was significantly higher in liver disease patients compared to healthy volunteers both in fasting and postprandial conditions (p<0.001). Changes in LS were significantly correlated with changes in PV flow (Spearman rho = 0.48, p = 0.013).

Conclusions

Caloric intake had no/minimal/large impact on diffusion/stiffness/portal vein flow, respectively. PC MRI and MRE but not DWI should be performed in controlled fasting state.     

In Vivo Correlation of Glucose Metabolism,Cell Density and Microcirculatory Parameters in Patients with Head and Neck Cancer: Initial Results Using Simultaneous PET/MRI

Objective

To demonstrate the feasibility of simultaneous acquisition of ¹⁸F-FDG-PET, diffusion-weighted imaging (DWI) and T1-weighted dynamic contrast-enhanced MRI (T1w-DCE) in an integrated simultaneous PET/MRI in patients with head and neck squamous cell cancer (HNSCC) and to investigate possible correlations between these parameters.

Methods

17 patients that had given informed consent (15 male, 2 female) with biopsy-proven HNSCC underwent simultaneous ¹⁸F-FDG-PET/MRI including DWI and T1w-DCE. SUV_max, SUV_mean, ADC_mean, ADC_min and K ^trans, k _ep and v _e were measured for each tumour and correlated using Spearman’s ρ.

Results

Significant correlations were observed between SUV_mean and K ^trans (ρ = 0.43; p ≤ 0.05); SUV_mean and k _ep (ρ = 0.44; p ≤ 0.05); K ^trans and k _ep (ρ = 0.53; p ≤ 0.05); and between k _ep and v _e (ρ = -0.74; p ≤ 0.01). There was a trend towards statistical significance when correlating SUV_max and ADC_min (ρ = -0.35; p = 0.08); SUV_max and K ^trans (ρ = 0.37; p = 0.07); SUV_max and k _ep (ρ = 0.39; p = 0.06); and ADC_mean and v _e (ρ = 0.4; p = 0.06).

Conclusion

Simultaneous ¹⁸F-FDG-PET/MRI including DWI and T1w-DCE in patients with HNSCC is feasible and allows depiction of complex interactions between glucose metabolism, microcirculatory parameters and cellular density.     

Differentiation of Central Lung Cancer from Atelectasis: Comparison of Diffusion-Weighted MRI with PET/CT

Objective

Prospectively assess the performance of diffusion-weighted magnetic resonance imaging (DW-MRI) for differentiation of central lung cancer from atelectasis.

Materials and Methods

38 consecutive lung cancer patients (26 males, 12 females; age range: 28–71 years; mean age: 49 years) who were referred for thoracic MR imaging examinations were enrolled. MR examinations were performed using a 1.5-T clinical scanner and scanning sequences of T1WI, T2WI, and DWI. Cancers and atelectasis were measured by mapping of the apparent diffusion coefficients (ADCs) obtained with a b-value of 500 s/mm².

Results

PET/CT and DW-MR allowed differentiation of tumor and atelectasis in all 38 cases, but T2WI did not allow differentiation in 9 cases. Comparison of conventional T2WI and DW-MRI indicated a higher contrast noise ratio of the central lung carcinoma than the atelectasis by DW-MRI. ADC maps indicated significantly lower mean ADC in the central lung carcinoma than in the atelectasis (1.83±0.58 vs. 2.90±0.26 mm²/s, p<0.0001). ADC values of small cell lung carcinoma were significantly greater than those from squamous cell carcinoma and adenocarcinoma (p<0.0001 for both).

Conclusions

DW-MR imaging provides valuable information not obtained by conventional MR and may be useful for differentiation of central lung carcinoma from atelectasis. Future developments may allow DW-MR imaging to be used as an alternative to PET-CT in imaging of patients with lung cancer.     

Image Derived Input Function for [18F]-FEPPA: Application to Quantify Translocator Protein (18 kDa) in the Human Brain

In [¹⁸F]-FEPPA positron emission topography (PET) imaging, automatic blood sampling system (ABSS) is currently the gold standard to obtain the blood time activity curve (TAC) required to extract the input function (IF). Here, we compare the performance of two image-based methods of IF extraction to the ABSS gold standard method for the quantification of translocator protein (TSPO) in the human brain. The IFs were obtained from a direct delineation of the internal carotid signal (CS) and a new concept of independent component analysis (ICA). PET scans were obtained from 18 healthy volunteers. The estimated total distribution volume (V_T) by CS-IF and ICA-IF were compared to the reference V_T obtained by ABSS-IF in the frontal and temporal cortex, cerebellum, striatum and thalamus regions. The V_T values estimated using ICA-IF were more reliable than CS-IF for all brain regions. Specifically, the slope regression in the frontal cortex with ICA-IF was r² = 0.91 (p<0.05), and r² = 0.71 (p<0.05) using CS-IF.     

Brain Changes in Long-Term Zen Meditators Using Proton Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging: A Controlled Study

Introduction

This work aimed to determine whether ¹H magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) are correlated with years of meditation and psychological variables in long-term Zen meditators compared to healthy non-meditator controls.

Materials and Methods

Design. Controlled, cross-sectional study. Sample. Meditators were recruited from a Zen Buddhist monastery. The control group was recruited from hospital staff. Meditators were administered questionnaires on anxiety, depression, cognitive impairment and mindfulness. ¹H-MRS (1.5 T) of the brain was carried out by exploring four areas: both thalami, both hippocampi, the posterior superior parietal lobule (PSPL) and posterior cingulate gyrus. Predefined areas of the brain were measured for diffusivity (ADC) and fractional anisotropy (FA) by MR-DTI.

Results

Myo-inositol (mI) was increased in the posterior cingulate gyrus and Glutamate (Glu), N-acetyl-aspartate (NAA) and N-acetyl-aspartate/Creatine (NAA/Cr) was reduced in the left thalamus in meditators. We found a significant positive correlation between mI in the posterior cingulate and years of meditation (r = 0.518; p = .019). We also found significant negative correlations between Glu (r = −0.452; p = .045), NAA (r = −0.617; p = .003) and NAA/Cr (r = −0.448; P = .047) in the left thalamus and years of meditation. Meditators showed a lower Apparent Diffusion Coefficient (ADC) in the left posterior parietal white matter than did controls, and the ADC was negatively correlated with years of meditation (r = −0.4850, p = .0066).

Conclusions

The results are consistent with the view that mI, Glu and NAA are the most important altered metabolites. This study provides evidence of subtle abnormalities in neuronal function in regions of the white matter in meditators.     

Correlations between Functional Imaging Markers Derived from PET/CT and Diffusion-Weighted MRI in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma

Objectives

To investigate the correlations between functional imaging markers derived from positron emission tomography/computed tomography (PET/CT) and diffusion-weighted magnetic resonance imaging (DWI) in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Further to compare the usefulness of these tumor markers in differentiating diagnosis of the two common types of Non-Hodgkin''s lymphoma (NHL).

Materials and Methods

Thirty-four consecutive pre-therapy adult patients with proven NHL (23 DLBCL and 11 FL) underwent PET/CT and MRI examinations and laboratory tests. The maximum standardized uptake value (SUV_max), metabolic tumor volume (MTV), and metabolic tumor burden (MTB) were determined from the PET/CT images. DWI was performed in addition to conventional MRI sequences using two b values (0 and 800 s/mm²). The minimum and mean apparent diffusion coefficient (ADC_min and ADC_mean) were measured on the parametric ADC maps.

Results

The SUV_max correlated inversely with the ADC_min (r = −0.35, p<0.05). The ADC_min, ADC_mean, serum thymidine kinase (TK), Beta 2-microglobulin (B2m), lactate dehydrogenase (LD), and C-reactive protein (CRP) correlated with both whole-body MTV and whole-body MTB (p<0.05 or 0.01). The SUV_max, TK, LD, and CRP were significantly higher in the DLBCL group than in the FL group. Receiver operating characteristic curve analysis showed that they were reasonable predictors in differentiating DLBCL from FL.

Conclusions

The functional imaging markers determined from PET/CT and DWI are associated, and the SUV_max is superior to the ADC_min in differentiating DLBCL from FL. All the measured serum markers are associated with functional imaging markers. Serum LD, TK, and CRP are useful in differentiating DLBCL from FL.     

High b Value (2,000 s/mm2) Diffusion-Weighted Magnetic Resonance Imaging in Prostate Cancer at 3 Tesla: Comparison with 1,000 s/mm2 for Tumor Conspicuity and Discrimination of Aggressiveness

Objective

The objective of our study was to investigate tumor conspicuity and the discrimination potential for tumor aggressiveness on diffusion-weighted magnetic resonance imaging (DW-MRI) with high b value at 3-T.

Materials and Methods

The institutional review board approved this study and waived the requirement for informed consent. A total of 50 patients with prostate cancer (69 cancer foci; 48 in the PZ, 20 in the TZ, and one in whole prostate) who underwent multiparametric prostate MRI including DW-MRI (b values: 0, 1000 s/mm² and 0, 2000 s/mm²) on a 3-T system were included. Lesion conspicuity score (LCS) using visual assessment (1 = invisible for surrounding normal site; 2 = slightly high intensity; 3 = moderately high; and 4 = very high) and tumor-normal signal intensity ratio (TNR) were assessed, and apparent diffusion coefficient (ADC, ×10⁻³ mm²/s) of the tumor regions and normal regions were measured.

Results

Mean LCS and TNR at 0, 2000 s/mm² was significantly higher than those at 0, 1000 s/mm² (p<0.001 for both). In addition, ADC at both 0, 1000 and 0, 2000 s/mm² was found to distinguish intermediate or high risk cancer with Gleason score ≥7 from low risk cancer with Gleason score ≤6 (p<0.001 for both). Furthermore, ADC of tumor regions correlated with Gleason score at both 0, 1000 s/mm² (ρ = −0.602; p<0.001) and 0, 2000 s/mm² (ρ = −0.645; p<0.001).

Conclusions

For tumor conspicuity and characterization of prostate cancer on DW-MRI of 3-T MRI, b = 0, 2000 s/mm² is more useful than b = 0, 1000 s/mm².     

Prognostic Value of FDG PET Imaging in Patients with Laryngeal Cancer

Background and Purpose

To investigate the prognostic value of ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with laryngeal cancer.

Materials and Methods

The study included 51 patients of whom 30 underwent definitive radiotherapy with or without chemotherapy and 21 underwent radical surgery with or without adjuvant chemoradiation therapy. FDG uptake by both the primary lesion and the neck node was measured using the maximum standardized uptake value (SUVmax). The effects of clinicopathological factors including primary tumor SUVmax and nodal SUVmax on progression-free survival, local control, nodal progression-free survival, and distant metastasis-free survival were evaluated using the log-rank test and Cox method.

Results

The median duration of follow-up was 48.6 months (range 8 to 82.1 months). Univariate analysis showed that nodal SUVmax, N status, and tumor TNM stage were significantly associated with recurrence, whereas primary tumor SUVmax, age, treatment strategy and T status were not. Multivariate analysis demonstrated that only the nodal SUVmax was a significantly unfavorable factor for progression-free survival (p = 0.029, hazard ratio 0.54, 95% CI 0.38-0.87) and nodal progression-free survival (p = 0.023, hazard ratio 0.51, 95% CI 0.34-0.81). ROC curve analysis and log-rank test showed that patients with a high nodal SUVmax (≧4) had a significantly lower progression-free survival rate than those with a low SUVmax (<4; p<0.0001).

Conclusions

The pretreatment SUVmax of nodal disease in patients with laryngeal cancer is prognostic for recurrence.     

Brain MRI CO2 Stress Testing: A Pilot Study in Patients with Concussion

Background

There is a real need for quantifiable neuro-imaging biomarkers in concussion. Here we outline a brain BOLD-MRI CO₂ stress test to assess the condition.

Methods

This study was approved by the REB at the University of Manitoba. A group of volunteers without prior concussion were compared to post-concussion syndrome (PCS) patients – both symptomatic and recovered asymptomatic. Five 3-minute periods of BOLD imaging at 3.0 T were studied – baseline 1 (BL1– at basal CO₂ tension), hypocapnia (CO₂ decreased ∼5 mmHg), BL2, hypercapnia (CO₂ increased ∼10 mmHg) and BL3. Data were processed using statistical parametric mapping (SPM) for 1^st level analysis to compare each subject’s response to the CO₂ stress at the p = 0.001 level. A 2^nd level analysis compared each PCS patient’s response to the mean response of the control subjects at the p = 0.05 level.

Results

We report on 5 control subjects, 8 symptomatic and 4 asymptomatic PCS patients. Both increased and decreased response to CO₂ was seen in all PCS patients in the 2^nd level analysis. The responses were quantified as reactive voxel counts: whole brain voxel counts (2.0±1.6%, p = 0.012 for symptomatic patients for CO₂ response < controls and 3.0±5.1%, p = 0.139 for CO₂ response > controls: 0.49±0.31%, p = 0.053 for asymptomatic patients for CO₂ response < controls and 4.4±6.8%, p = 0.281 for CO₂ response > controls).

Conclusions

Quantifiable alterations in regional cerebrovascular responsiveness are present in concussion patients during provocative CO₂ challenge and BOLD MRI and not in healthy controls. Future longitudinal studies must aim to clarify the relationship between CO₂ responsiveness and individual patient symptoms and outcomes.     

Quantitative Apparent Diffusion Coefficient Measurements Obtained by 3-Tesla MRI Are Correlated with Biomarkers of Bladder Cancer Proliferative Activity

Purpose

To investigate the association between Apparent Diffusion Coefficient (ADC) values and cell cycle and proliferative biomarkers (p53, p21, Ki67,) in order to establish its potential role as a noninvasive biomarker for prediction of cell cycle, proliferative activity and biological aggressiveness in bladder cancer.

Materials and Methods

Patients with bladder cancer who underwent 3,0 Tesla DW-MRI of the bladder before TUR-B or radical cystectomy were eligible for this prospective IRB-approved study. Histological specimen were immunohistochemically stained for the following markers: p53, p21 and ki67. Two board-certified uropathologists reviewed the specimens blinded to DW-MRI results. Histological grade and T-stage were classified according to the WHO 2004 and the 2009 TNM classification, respectively. Nonparametric univariate and multivariate statistics including correlation, logistic regression and ROC analysis were applied.

Results

Muscle invasive bladder cancer was histologically confirmed in 10 out of 41 patients. All examined tissue biomarkers were significantly correlated with ADC values (p<0.05, respectively). Based on multivariate analysis, p53 and ADC are both independent prognostic factors for muscle invasiveness of bladder cancer (>/ = T2). (p = 0.013 and p = 0.018).

Conclusion

ADC values are associated with cell cycle and proliferative biomarkers and do thereby reflect invasive and proliferative potential in bladder cancer. ADC and p53 are both independent prognostic factors for muscle invasiveness in bladder cancer.     

Glioma: Application of Whole-Tumor Texture Analysis of Diffusion-Weighted Imaging for the Evaluation of Tumor Heterogeneity

Background and Purpose

To apply a texture analysis of apparent diffusion coefficient (ADC) maps to evaluate glioma heterogeneity, which was correlated with tumor grade.

Materials and Methods

Forty patients with glioma (WHO grade II (n = 8), grade III (n = 10) and grade IV (n = 22)) underwent diffusion-weighted imaging (DWI), and the corresponding ADC maps were obtained. Regions of interest containing the lesions were drawn on every section of the ADC map containing the tumor, and volume-based data of the entire tumor were constructed. Texture and first order features including entropy, skewness and kurtosis were derived from the ADC map using in-house software. A histogram analysis of the ADC map was also performed. The texture and histogram parameters were compared between low-grade and high-grade gliomas using an unpaired student’s t-test. Additionally, a one-way analysis of variance analysis with a post-hoc test was performed to compare the parameters of each grade.

Results

Entropy was observed to be significantly higher in high-grade gliomas than low-grade tumors (6.861±0.539 vs. 6.261±0.412, P  = 0.006). The fifth percentiles of the ADC cumulative histogram also showed a significant difference between high and low grade gliomas (836±235 vs. 1030±185, P = 0.037). Only entropy proved to be significantly different between grades III and IV (6.295±0.4963 vs. 7.119±0.3165, P<0.001). The diagnostic accuracy of ADC entropy was significantly higher than that of the fifth percentile of the ADC histogram (P = 0.0034) in distinguishing high- from low-grade glioma.

Conclusion

A texture analysis of the ADC map based on the entire tumor volume can be useful for evaluating glioma grade, which provides tumor heterogeneity.     

Correlation of the Apparent Diffusion Coefficient (ADC) with the Standardized Uptake Value (SUV) in Lymph Node Metastases of Non-Small Cell Lung Cancer (NSCLC) Patients Using Hybrid 18F-FDG PET/MRI

ObjectiveTo compare the apparent diffusion coefficient (ADC) in lymph node metastases of non-small cell lung cancer (NSCLC) patients with standardized uptake values (SUV) derived from combined 18F-fluoro-deoxy-glucose-positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI).ResultsA total of 146 suspicious lymph nodes were found in 25 patients. One hundred lymph nodes were eligible for final analysis. Ninety-one lymph nodes were classified as malignant and 9 as benign according to the reference standard. In malignant lesions, mean SUV_max was 9.1 ± 3.8 and mean SUV_mean was 6.0 ± 2.5 while mean ADC_mean was 877.0 ± 128.6 x10^-5 mm²/s in PET/MRI. For all malignant lymph nodes, a weak, inverse correlation between SUV_max and ADC_mean as well as SUV_mean and ADC_mean (r = -0.30, p<0.05 and r = -0.36, p<0.05) existed.ConclusionThe present data show a weak inverse correlation between increased glucose-metabolism and cellularity in lymph node metastases of NSCLC patients. 18F-FDG-PET and DWI thus may offer complementary information for the evaluation of treatment response in lymph node metastases of NSCLC.     

Correlations Between DCE MRI and Histopathological Parameters in Head and Neck Squamous Cell Carcinoma

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) can characterize perfusion and vascularization of tissues. DCE MRI parameters can differentiate between malignant and benign lesions and predict tumor grading. The purpose of this study was to correlate DCE MRI findings and various histopathological parameters in head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Sixteen patients with histologically proven HNSCC (11 cases primary tumors and in 5 patients with local tumor recurrence) were included in the study. DCE imaging was performed in all cases and the following parameters were estimated: K^trans, V_e, K_ep, and iAUC. The tumor proliferation index was estimated on Ki 67 antigen stained specimens. Microvessel density parameters (stained vessel area, total vessel area, number of vessels, and mean vessel diameter) were estimated on CD31 antigen stained specimens. Spearman''s non-parametric rank sum correlation coefficients were calculated between DCE and different histopathological parameters. RESULTS: The mean values of DCE perfusion parameters were as follows: K^trans 0.189 ± 0.056 min⁻¹, K_ep 0.390 ± 0.160 min⁻¹, V_e 0.548 ± 0.119%, and iAUC 22.40 ± 12.57. Significant correlations were observed between K_ep and stained vessel areas (r = 0.51, P = .041) and total vessel areas (r = 0.5118, P = .043); between V_e and mean vessel diameter (r = −0.59, P = .017). Cell count had a tendency to correlate with V_e (r = −0.48, P = .058). In an analysis of the primary HNSCC only, a significant inverse correlation between K^trans and KI 67 was identified (r = −0.62, P = .041). Our analysis showed significant correlations between DCE parameters and histopathological findings in HNSCC.Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) has been reported as a technique which is able to characterize perfusion and vascularization of tissues [1], [2]. It has been shown that DCE MRI can be helpful to differentiate between malignant and benign lesions [1]. For example, Yuan et al. reported that lung cancer had a larger volume transfer constant (K^trans) and a lower volume of the extravascular extracellular leakage space (V_e) in comparison to benign lesions [3]. Similar results were reported by Li et al. for breast lesions [4]. Furthermore, according to Cho et al., DCE MRI parameters can be used to distinguish prostatic cancer from benign changes [5]. Moreover, DCE MRI parameters can also predict tumor grading. As reported previously, K^trans correlated well with Gleason score in prostatic cancer [5], [6]. According to other reports, K^trans and V_e correlated with glioma grade [7], [8].DCE MRI parameters were also associated with prognosis in several malignancies [9], [10]. Koo et al. showed that breast cancers with higher K^trans or lower V_e had poor prognostic factors and were often of the triple-negative subtype [10].According to the literature, DCE MRI parameters can predict response to therapy in different tumors. For instance, some authors mentioned that low pretreatment K^trans in regional lymph node metastases in head and neck cancer was associated with a poor response to concurrent chemoradiation therapy [11].Furthermore, Andersen et al. showed that DCE MR parameters obtained prior to chemoradiotherapy predicted survival of patients with cervical cancer [12].Presumably, DCE MRI parameters may be based on tissue composition, such as cellularity and vascular density. However, in this regard there are contradictory data in the literature. While some studies identified significant correlations between DCE MRI and histopathological parameters, others did not [13], [14], [15], [16].The purpose of this study was to correlate DCE MRI findings and various histopathological parameters in head and neck squamous cell carcinoma (HNSCC).