Texture Analysis of T2-Weighted MR Images to Assess Acute Inflammation in Brain MS Lesions.

Brain blood barrier breakdown as assessed by contrast-enhanced (CE) T1-weighted MR imaging is currently the standard radiological marker of inflammatory activity in multiple sclerosis (MS) patients. Our objective was to evaluate the performance of an alternative model assessing the inflammatory activity of MS lesions by texture analysis of T2-weighted MR images. Twenty-one patients with definite MS were examined on the same 3.0T MR system by T2-weighted, FLAIR, diffusion-weighted and CE-T1 sequences. Lesions and mirrored contralateral areas within the normal appearing white matter (NAWM) were characterized by texture parameters computed from the gray level co-occurrence and run length matrices, and by the apparent diffusion coefficient (ADC). Statistical differences between MS lesions and NAWM were analyzed. ROC analysis and leave-one-out cross-validation were performed to evaluate the performance of individual parameters, and multi-parametric models using linear discriminant analysis (LDA), partial least squares (PLS) and logistic regression (LR) in the identification of CE lesions. ADC and all but one texture parameter were significantly different within white matter lesions compared to within NAWM (p < 0.0167). Using LDA, an 8-texture parameter model identified CE lesions with a sensitivity Se = 70% and a specificity Sp = 76%. Using LR, a 10-texture parameter model performed better with Se = 86% / Sp = 84%. Using PLS, a 6-texture parameter model achieved the highest accuracy with Se = 88% / Sp = 81%. Texture parameter from T2-weighted images can assess brain inflammatory activity with sufficient accuracy to be considered as a potential alternative to enhancement on CE T1-weighted images.

Dynamic contrast-enhanced computed tomography to assess early activity of cetuximab in squamous cell carcinoma of the head and neck.

BACKGROUND: Cetuximab, a monoclonal antibody targeting the Epidermal Growth Factor Receptor (EGFR), has demonstrated activity in various tumor types. Using dynamic contrast-enhanced computed tomography (DCE-CT), we investigated the early activity of cetuximab monotherapy in previously untreated patients with squamous cell carcinoma of the head and neck (SCCHN). METHODS: Treatment-naïve patients with SCCHN received cetuximab for 2 weeks before curative surgery. Treatment activity was evaluated by DCE-CT at baseline and before surgery. Tumor vascular and interstitial characteristics were evaluated using the Brix two-compartment kinetic model. Modifications of the perfusion parameters (blood flow Fp, extravascular space ve, vascular space vp, and transfer constant PS) were assessed between both time points. DCE data were compared to FDG-PET and histopathological examination obtained simultaneously. Plasmatic vascular markers were investigated at different time points. RESULTS: Fourteen patients had evaluable DCE-CT parameters at both time points. A significant increase in the extravascular extracellular space ve accessible to the tracer was observed but no significant differences were found for the other kinetic parameters (Fp, vp or PS). Significant correlations were found between DCE parameters and the other two modalities. Plasmatic VEGF, PDGF-BB and IL-8 decreased as early as 2 hours after cetuximab infusion. CONCLUSIONS: Early activity of cetuximab on tumor interstitial characteristics was detected by DCE-CT. Modifications of plasmatic vascular markers are not sufficient to confirm anti-angiogenic cetuximab activity in vivo. Further investigation is warranted to determine to what extent DCE-CT parameters are modified and to evaluate whether they are able to predict treatment outcome.

Congenital horner syndrome with heterochromia iridis associated with ipsilateral internal carotid artery hypoplasia.

BACKGROUND: Horner syndrome (HS), also known as Claude-Bernard-Horner syndrome or oculosympathetic palsy, comprises ipsilateral ptosis, miosis, and facial anhidrosis. CASE REPORT: We report herein the case of a 67-year-old man who presented with congenital HS associated with ipsilateral hypoplasia of the internal carotid artery (ICA), as revealed by heterochromia iridis and confirmed by computed tomography (CT). CONCLUSIONS: CT evaluation of the skull base is essential to establish this diagnosis and distinguish aplasia from agenesis/hypoplasia (by the absence or hypoplasia of the carotid canal) or from acquired ICA obstruction as demonstrated by angiographic CT.

Enhanced choline metabolism in a rodent rhabdomyosarcoma model: correlation between RT-PCR and translational 3 T H-MRS.

PURPOSE: To investigate which transmembrane choline transporters and intracellular choline kinases play a prominent role at gene expression level in the rise of the total choline (tCho) peak at proton MR spectra in a rodent rhabdomyosarcoma model. MATERIALS AND METHODS: Twenty-two rats bearing grafted bilateral syngenic rhabdomyosarcoma were examined on a clinical 3 T MR system. Total choline concentration was measured from proton MR spectra using cubic centimeter volumes of interest (VOIs) located contiguously along the greater axis of the tumour. After euthanasia, cubic centimetre tissue specimens corresponding to Proton magnetic resonance spectroscopy (H-MRS) VOIs were frozen in liquid nitrogen. Out of 89 H-MRS voxels, only 39 with a corresponding tissue specimen suitable for biochemical processing were included in the analysis. RNA was extracted from all the 39 samples and reverse-transcribed into cDNA. Choline kinase α and ß gene expression as well as genes of the transmembrane transporters OCT1, OCT2, OCT3, CTL1, CTL3, CTL4 and CHT1 were studied using reverse transcriptase polymerase chain reaction. The expression level of each gene (ΔCt), was normalized referred to that of the RPL19 gene. The Spearman rank correlation coefficient was used to analyse variables. RESULTS: There was no overexpression of genes coding for kinases; however, significant correlation was observed between kinase α sub-type and the tCho peak (P=.002; r=0.51). OCT1 was the most overexpressed transporter gene. Less overexpressed CTL1 gene was significantly correlated with the tCho peak (P=.02; r=0.38). CONCLUSION: Choline transporters seem to play a predominant role in the increase in total choline concentration at the gene expression level in our model.

Early (72-hour) detection of radiotherapy-induced changes in an experimental tumor model using diffusion-weighted imaging, diffusion tensor imaging, and Q-space imaging parameters: a comparative study.

PURPOSE: To assess and compare the potential of various diffusion-related magnetic resonance imaging (MRI) parameters to detect early radiotherapy (RT)-induced changes in tumors. MATERIALS AND METHODS: Nineteen tumors in a rat model were imaged on a clinical 3T system before and 72 hours after a single RT session. Diffusion imaging was performed using an echo planar sequence containing 16 b-factors and six gradient directions. This allowed us to perform a tensor analysis of mono- and biexponential decays and a q-space analysis. Parametric maps (both trace and fractional anisotropy) were reconstructed for: 2-point apparent diffusion coefficient (ADC), 16-point ADC, biexponential amplitudes and ADCs, and height, width, and kurtosis of the probability density function (PDF). A texture analysis yielded quantities such as average and contrast. The sensitivity of diffusion-related parameters was quantified in terms of the mean relative difference (when comparing pre- and post-RT status). RESULTS: Traces and anisotropies display differences in response to RT. Average traces are most sensitive for ADCs and kurtosis. Average anisotropies are all very sensitive except the slow biexponential component. The best contrast (traces) was found for the ADCs and the width of the PDF. CONCLUSION: ADC performed well, but high b-values analysis added extra sensitive parameters for monitoring early RT-induced changes.

Early monitoring of external radiation therapy by [18F]-fluoromethylcholine positron emission tomography and 3-T proton magnetic resonance spectroscopy: an experimental study in a rodent rhabdomyosarcoma model.

PURPOSE: To assess early radiation therapy (RT)-induced variations in total choline (tCho) concentration measured by proton magnetic resonance spectroscopy (H-MRS) and in (18)F-labelled fluoromethylcholine (FCH) uptake measured by PET in a rodent tumour model. METHODS: Nine rats bearing syngenic rhabdomyosarcoma grafts in both thighs were irradiated (13 Gy, one fraction). H-MRS data and FCH-PET were acquired in the same imaging session prior to and 3, 9 and 16 days after external RT. Total choline concentration was expressed in arbitrary units as the area under the curve of the 3.2-ppm peak on H-MR spectra. FCH uptake was expressed as maximum standardized uptake value (SUV(max)) and as the % of injected dose per gram (%ID/g) after precise tumour delineation on hybrid PET-MR images. Pre- and post-RT data were compared using the Student's paired t test, and results were expressed as mean+/-S.D. RESULTS: Seventeen tumours were available for analysis. A mean drop in choline concentration of 45% was observed 3 days after irradiation (P<.001), whereas a concomitant mean increase in SUV(max) of 41% was observed (P=.006). Choline concentration reincreased on later time points. CONCLUSIONS: Opposite trend between increased FCH uptake and decreased tCho peak was observed at 3 days. Later (9 and 16 days), uptake remained stable and tCho peak reincreased.

Phase II study of sunitinib in recurrent or metastatic squamous cell carcinoma of the head and neck: GORTEC 2006-01.

PURPOSE To assess the efficacy and toxicity of sunitinib monotherapy in palliative squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS Thirty-eight patients with SCCHN having evidence of progressive disease (PD) were treated with sunitinib 37.5 mg/d given continuously until PD or unacceptable toxicity. The primary end point was the rate of disease control, defined as stable disease (SD) or partial response (PR) at 6 to 8 weeks after treatment initiation (two-stage design, Simon). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed in a subset of patients before and 6 to 8 weeks after treatment. The volume transfer constant of the contrast agent (K(trans)) was used to measure changes in the microcirculation blood flow and endothelial permeability of the tumor. Results A PR was observed in one patient, SD in 18, and PD in 19 (Response Evaluation Criteria in Solid Tumors [RECIST]), resulting in a disease control rate of 50%. Among the 18 patients with SD, there were five unconfirmed PRs and six additional minor responses. A significant decrease in K(trans) was seen in three of the four patients who received DCE-MRI monitoring. Grade 5 head and neck bleeds occurred in four patients. Local complications, including the appearance or worsening of tumor skin ulceration or tumor fistula, were recorded in 15 patients. CONCLUSION Sunitinib demonstrated modest activity in palliative SSCHN. The severity of some of the complications highlights the importance of improved patient selection for future studies with sunitinib in head and neck cancer. Sunitinib should not be used outside clinical trials in SSCHN.

Rodent rhabdomyosarcoma: comparison between total choline concentration at H-MRS and [18F]-fluoromethylcholine uptake at PET using accurate methods for collecting data.

PURPOSE: To compare choline concentration/amount at proton magnetic resonance spectroscopy (H-MRS) and [18F]-fluoromethylcholine (FCH) uptake at positron emission tomography (PET) in a tumour animal model. PROCEDURES: Twenty-two rats bearing grafted syngenic rhabdomyosarcoma in both thighs were examined on a 3T MR system and on a small animal PET system. Total choline concentration was measured on proton MR spectra using a so-called 'best internal fitting' volume of interest. Choline uptake was expressed as mean and maximum standardized uptake value (SUV and SUVmax, respectively) and as the percent of injected dose (%ID) after tumour delineation on fused PET-MR images. Data sets were displayed on standard scatter plots. RESULTS: Thirty-six tumours were available for analysis. The area under the curve of the 3.2 ppm choline peak ranged from 69 to 476 (mean, 192) in arbitrary units. Mean SUV values ranged from 0.05 to 0.49 (mean, 0.19) and the %ID from 0.05 to 2.28 (mean, 0.54). Scatter plots failed to reveal quantitative relationship between choline concentration and uptake. Empirically data-driven cut-off lines applied to choline amount (choline concentration x tumour volume) versus choline uptake suggested a paradoxically negative relationship. CONCLUSION: Total choline concentration did not correlate with FCH uptake in a tumour experimental model. A negative feedback of high values of total choline amount on cellular FCH uptake seemed to be present.

Alginate moulding: an empirical method for magnetic resonance imaging/positron emission tomography co-registration in a tumor rat model.

BACKGROUND AND PURPOSE: In the experimental field of animal models, co-registration between positron emission tomography (PET) and magnetic resonance imaging (MRI) data still relies on non-automated post-processing using sophisticated algorithms and software developments. We assessed the value of an empirical method using alginate moulding for PET-MR co-registration in a tumor rat model. METHODS: Male WAG/RijHsd rats bearing grafted syngenic rhabdomyosarcoma were examined under general anesthesia by MRI using a clinical whole-body 3-T system equipped with a sensitivity-encoding four-channel wrist coil and by a small animal PET system using labelled [(18)F]-fluorocholine as tracer. An alginate mould including a system of external fiducials was manufactured for each animal, allowing strict immobilization and similar positioning for both modalities. Fourteen rats (27 tumors) had only one MR/PET imaging session. Five rats (9 tumors) had a similar MR/PET session before and 3 days after external radiation therapy (13 Gy in one fraction) using the same mould. Co-registration was performed using the Pmod release 2.75 software (PMOD Technologies, Ltd., Adliswil, Switzerland) with mutual information algorithm. RESULTS: The manufacture of the alginate moulds was easy and innocuous. Imaging sessions were well tolerated. PET-MR co-registration based on mutual information was perfect at visual examination, which was confirmed by the superimposition of external fiducials on fused images. Reuse of the same mould for the post-therapeutic session was feasible 3 days after the pre-therapeutic one in spite of tumor growth. CONCLUSION: The empirical method using alginate moulding with external fiducials for PET-MR co-registration in a rodent tumor model was feasible and accurate.

Lateral sacral artery aneurysm: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: We report the third case of an aneurysm of the lateral sacral artery (AnLSA). In all cases, because of an incorrect preoperative diagnosis, the surgeons were confronted with severe and unexpected hemorrhaging, and surgery was aborted without effective treatment. Our purpose is to present the preoperative features of AnLSA and its treatment modalities. CLINICAL PRESENTATION: A 54-year-old man had a medical history of renal transplantation on his left external iliac artery. He complained of acute lumbar pain associated with cauda equina syndrome, which resolved within a few hours. At that time, a magnetic resonance imaging (MRI) scan revealed an intracanal hematoma extending from S1 to T12. Six weeks later, a second MRI scan demonstrated an oval-shaped intracanal mass behind the vertebral body of S1 with intense gadolinium enhancement. INTERVENTION: An anterior epidural mass was found. An incision into this mass resulted in significant arterial hemorrhaging. Transparietal embolization with a cotton compress and closure of the aneurysm wall were performed. The postoperative clinical status was stable, and a delayed angiographic study suggested a diagnosis of aneurysm of the right LSA, a branch of the internal iliac artery. Its pathophysiology was explained by the development of a high-flow transpelvic shunt from the right iliac artery territory to the left, to maintain the renal graft blood flow that had initially been reduced by stenosis of the left common iliac artery. Six weeks later, a new MRI scan demonstrated that the AnLSA had increased in size. The lesion was then excluded endovascularly by injection of glue. CONCLUSION: A medical history of renal transplantation with MRI scans showing an anterior epidural mass behind S1 or a spontaneous spinal epidural hematoma are features that must evoke a diagnosis of AnLSA. Treatment is mandatory and is best achieved by embolization. Surgery based on angiographic findings is indicated if the lesion is responsible for a compressive hematoma.

Surgical treatment of a syringomyelia associated with an idiopathic arachnoid malformation disclosed by preoperative MRI.

BACKGROUND: We describe the very rare condition of an idiopathic spinal arachnoid malformation associated with syringomyelia (SM) and depicted on preoperative magnetic resonance imaging (MRI) whose features were confirmed at surgery. CASE DESCRIPTION: A 34-year-old female suffered from progressive gait impairment because of lower limb palsy and sensory disturbances. MRI demonstrated a bulging membrane at the T6 level that was transversely stretched between the dorsal aspect of the spinal cord and the posterior dura mater. At this level, the spinal cord appeared atrophic and pushed anteriorly against the dura with enlargement of the posterior subarachnoid spaces (SAS) and focal collapse of an associated panmedullar SM. Surgery consisted in releasing the arachnoid malformation and opening the inferior segment of the syringomyelic cavity. Pathological examination revealed a fibro-sclerotic tissue with cellular areas of meningo-endothelial cells. Postoperative neurological status progressively improved but slightly. Three-months and 1 year postoperatively, MRI showed the collapse of the whole SM and restoration of cerebrospinal fluid (CSF) flow at the treated T6 level. CONCLUSION: Spinal arachnoid malformations associated with SM are very rare and have never been described up to now on MRI. Surgical removal of the causative malformation allows spinal cord decompression and prevents the recurrence of the SM by restoring normal CSF circulation.