Pål Erik Goa

Predicting survival and early clinical response to primary chemotherapy for patients with locally advanced breast cancer using DCE-MRI

To evaluate dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) as a tool for early prediction of response to neoadjuvant chemotherapy (NAC) and 5‐year survival in patients with locally advanced breast cancer.

Peripheral zone prostate cancer localization by multiparametric magnetic resonance at 3 T: unbiased cancer identification by matching to histopathology.

ObjectivesThe aim of this study was to assess the diagnostic accuracy of peripheral zone prostate cancer localization by multiparametric magnetic resonance (MR) at 3 T using segmental matching of histopathology and MR images to avoid bias by image features in selection of cancer and noncancer regions. Materials and MethodsForty-eight patients underwent multiparametric MR imaging (MRI) on a 3 T system using a phased array body coil and spine coil elements for signal detection before prostatectomy. The examination included T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), dynamic contrast-enhanced imaging (DCE-MRI), and MR spectroscopic imaging (MRSI). Histopathology slides were correlated to T2W images and a stringent matching procedure was performed to define cancer and noncancer areas of the peripheral zone without influence of the MR image appearance. Mean T2W signal intensity, apparent diffusion coefficient, area under the enhancement curve, and choline + creatine-to-citrate signal ratio were calculated for cancer and noncancer areas. Receiver operating characteristic (ROC) analysis was performed on MR-derived parameters from the selected areas. Logistic regression was used to create models based on best combination of parameters. A simplified approach assigning a parametric score to each segment based on cutoff values from ROC analysis was also explored. ResultsBy using the stringent matching procedure, 138 noncancer and 41 cancer segments were selected in the T2W images and transferred to the images of the other MR methods. A significant difference between mean values in cancer and noncancer segments was observed for all MR parameters analyzed (P < 0.001). Apparent diffusion coefficient was the best performing single parameter, with an area under the ROC curve Az,DWI of 0.90 for prostate cancer detection. Any combination of T2WI, DWI, and DCE-MRI was significantly better than T2WI alone in separating cancer from noncancer segments (Az,T2WI + DWI + DCE-MRI = 0.94, Az,T2WI + DWI = 0.92, Az,T2WI + DCE-MRI = 0.91, Az,T2WI = 0.85). The combination of T2WI and MRSI was also better than T2WI alone (Az, T2WI + MRSI = 0.90); however, the logistic regression models including MRSI did not have significant parameters. The simplified approach combining all parameters gave similar results to logistic regression combining all parameters (Az = 0.95 and 0.97, respectively). ConclusionBy selecting histopathology defined cancer and noncancer areas without influence of image contrast, this study objectively reveals that all investigated MR parameters have the ability to separate cancer from noncancer areas in the peripheral zone individually and that any combination is better than T2WI alone.

Manganese-enhanced MRI of the rat visual pathway : Acute neural toxicity, contrast enhancement, axon resolution, axonal transport and clearance of Mn2+

To provide dose‐response data for the safe and effective use of MnCl2 for manganese (Mn2+) ‐enhanced MRI (MEMRI) of the visual pathway.

Assessment of early docetaxel response in an experimental model of human breast cancer using DCE-MRI, ex vivo HR MAS, and in vivo1H MRS

The purpose of this study was to evaluate the use of dynamic contrast‐enhanced (DCE) MRI, in vivo 1H MRS and ex vivo high resolution magic angle spinning (HR MAS) MRS of tissue samples as methods to detect early treatment effects of docetaxel in a breast cancer xenograft model (MCF‐7) in mice. MCF‐7 cells were implanted subcutaneously in athymic mice and treated with docetaxel (20, 30, and 40 mg/kg) or saline six weeks later. DCE‐MRI and in vivo 1H MRS were performed on a 7 T MR system three days after treatment. The dynamic images were used as input for a two‐compartment model, yielding the vascular parameters Ktrans and ve. HR MAS MRS, histology, and immunohistochemical staining for proliferation (Ki‐67), apoptosis (M30 cytodeath), and vascular/endothelial cells (CD31) were performed on excised tumor tissue. Both in vivo spectra and HR MAS spectra were used as input for multivariate analysis (principal component analysis (PCA) and partial least squares regression analysis (PLS)) to compare controls to treated tumors. Tumor growth was suppressed in docetaxel‐treated mice compared to the controls. The anti‐tumor effect led to an increase in Ktrans and ve values in all the treated groups. Furthermore, in vivo MRS and HR MAS MRS revealed a significant decrease in choline metabolite levels for the treated groups, in accordance with reduced proliferative index as seen on Ki‐67 stained sections. In this study DCE‐MRI, in vivo MRS and ex vivo HR MAS MRS have been used to demonstrate that docetaxel treatment of a human breast cancer xenograft model results in changes in the vascular dynamics and metabolic profile of the tumors. This indicates that these MR methods could be used to monitor intra‐tumoral treatment effects. Copyright

Dynamic contrast‐enhanced MRI texture analysis for pretreatment prediction of clinical and pathological response to neoadjuvant chemotherapy in patients with locally advanced breast cancer

The aim of this study was to investigate the potential of texture analysis, applied to dynamic contrast‐enhanced MRI (DCE‐MRI), to predict the clinical and pathological response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC) before NAC is started. Fifty‐eight patients with LABC were classified on the basis of their clinical response according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines after four cycles of NAC, and according to their pathological response after surgery. T1‐weighted DCE‐MRI with a temporal resolution of 1 min was acquired on a 3‐T Siemens Trio scanner using a dedicated four‐channel breast coil before the onset of treatment. Each lesion was segmented semi‐automatically using the 2‐min post‐contrast subtracted image. Sixteen texture features were obtained at each non‐subtracted post‐contrast time point using a gray level co‐occurrence matrix. Appropriate statistical analyses were performed and false discovery rate‐based q values were reported to correct for multiple comparisons. Statistically significant results were found at 1–3 min post‐contrast for various texture features for the prediction of both the clinical and pathological response. In particular, eight texture features were found to be statistically significant at 2 min post‐contrast, the most significant feature yielding an area under the curve (AUC) of 0.77 for response prediction for stable disease versus complete responders after four cycles of NAC. In addition, four texture features were found to be significant at the same time point, with an AUC of 0.69 for response prediction using the most significant feature for classification based on the pathological response. Our results suggest that texture analysis could provide clinicians with additional information to increase the accuracy of prediction of an individual response before NAC is started. Copyright

In vivo mapping of temporospatial changes in manganese enhancement in rat brain during epileptogenesis

Mesial temporal lobe epilepsy is associated with structural and functional abnormalities, such as hippocampal sclerosis and axonal reorganization. The temporal evolution of these changes remains to be determined, and there is a need for in vivo imaging techniques that can uncover the epileptogenic processes at an early stage. Manganese-enhanced magnetic resonance imaging may be useful in this regard. The aim of this study was to analyze the temporospatial changes in manganese enhancement in rat brain during the development of epilepsy subsequent to systemic kainate application (10 mg/kg i.p.). MnCl(2) was given systemically on day 2 (early), day 15 (latent), and 11 weeks (chronic phase) after the initial status epilepticus. Twenty-four hours after MnCl(2) injection T1-weighted 3D MRI was performed followed by analysis of manganese enhancement. In the medial temporal lobes, there was a pronounced decrease in manganese enhancement in CA1, CA3, dentate gyrus, entorhinal cortex and lateral amygdala in the early phase. In the latent and chronic phases, recovery of the manganese enhancement was observed in all these structures except CA1. A significant increase in manganese enhancement was detected in the entorhinal cortex and the amygdala in the chronic phase. In the latter phase, the structurally intact cerebellum showed significantly decreased manganese enhancement. The highly differentiated changes in manganese enhancement are likely to represent the net outcome of a number of pathological and pathophysiological events, including cell loss and changes in neuronal activity. Our findings are not consistent with the idea that manganese enhancement primarily reflects changes in glial cells.

Manganese-enhanced magnetic resonance imaging of hypoxic–ischemic brain injury in the neonatal rat

Hypoxic-ischemic injury (HI) to the neonatal brain results in delayed neuronal death with accompanying inflammation for days after the initial insult. The aim of this study was to depict delayed neuronal death after HI using Manganese-enhanced MRI (MEMRI) and to evaluate the specificity of MEMRI in detection of cells related to injury by comparison with histology and immunohistochemistry. 7-day-old Wistar rat pups were subjected to HI (occlusion of right carotid artery and 8% O(2) for 75 min). 16 HI (HI+Mn) and 6 sham operated (Sham+Mn) pups were injected with MnCl(2) (100 mM, 40 mg/kg) and 10 HI-pups (HI+Vehicle) received NaCl i.p. 6 h after HI. 3D T(1)-weighted images (FLASH) and 2D T(2)-maps (MSME) were acquired at 7 T 1, 3 and 7 days after HI. Pups were sacrificed after MR-scanning and brain slices were cut and stained for CD68, GFAP, MAP-2, Caspase-3 and Fluorojade B. No increased manganese-enhancement (ME) was detectable in the injured hemisphere on day 1 or 3 when immunohistochemistry showed massive ongoing neuronal death. 7 days after HI, increased ME was seen on T(1)-w images in parts of the injured cortex, hippocampus and thalamus among HI+Mn pups, but not among HI+Vehicle or Sham+Mn pups. Comparison with immunohistochemistry showed delayed neuronal death and inflammation in these areas with late ME. Areas with increased ME corresponded best with areas with high concentrations of activated microglia. Thus, late manganese-enhancement seems to be related to accumulation of manganese in activated microglia in areas of neuronal death rather than depicting neuronal death per se.

Prognostic value of pretreatment dynamic contrast-enhanced MR imaging in breast cancer patients receiving neoadjuvant chemotherapy: Overall survival predicted from combined time course and volume analysis:

Background: The prognostic value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in breast cancer has been explored, and the results are promising. Purpose: To investigate the possible correlation between pretreatment DCE-MRI and overall survival 5 years after diagnosis in breast cancer patients receiving neoadjuvant chemotherapy (NAC) using combined time course analysis and volume measurement from DCE-MRI data acquired with 1 min temporal resolution. Material and Methods: Pretreatment DCE-MR images of 32 female patients were examined. The total enhancing volume was calculated by including the voxels with >60% signal enhancing 1 min postcontrast. The signal intensity time course data were automatically classified on a voxel-by-voxel basis according to the enhancing characteristics: persistent (type I), plateau (type II) or washout (type III), and the resulting volumes of each enhancement type were calculated. Results: A significant correlation between total enhancing volume and 5-year survival was found, P=0.05 (log-rank). The survival was 51 ±15 months (mean ±95% confidence intervals (CI)) and 73±12 months in patients with a total enhancing volume >41 cm3 and ≤41 cm3, respectively. A two-dimensional discriminator, taking both total enhancing volume and type III enhancing volume into account, improved the prediction of survival, resulting in a P value (log-rank) between survivors and non-survivors of <0.001. The survival was 44±16 months (mean ±95% CI) and 74±11 months in patients with a total enhancing volume >58 cm3 and/or a type III volume >8 cm3, and ≤58 cm3 and ≤8 cm3, respectively. Conclusion: Pretreatment DCE-MRI might help in predicting prognosis in breast cancer patients receiving NAC.

Axon tracing in the adult rat optic nerve and tract after intravitreal injection of MnDPDP using a semiautomatic segmentation technique

To develop and validate an objective technique for 3D segmentation of manganese‐enhanced MR images of the optic nerve/tract (ON) in adult rats to improve contrast‐to‐noise (CNR) calculations and use the technique to ascertain if manganese dipyridoxyl diphosphate (MnDPDP) gives sufficient Mn2+ enhancement compared to MnCl2 when used for functional imaging of the visual pathway.

Inhomogeneous static magnetic field-induced distortion correction applied to diffusion weighted MRI of the breast at 3T.

To evaluate the performance of an advanced method for correction of inhomogeneous static magnetic field induced distortion in echo‐planar imaging (EPI), applied to diffusion‐weighted MRI (DWI) of the breast.