Sotirios Bisdas

Cervical lymph nodes

The lymph node staging is a very important prognostic parameter for patients with presenting with head neck cancer and is influencing the selection of the different therapeutic strategies including surgery, chemotherapy, radiotherapy or a combination of them. The accuracy of imaging techniques, such as US, MR imaging, and CT, depends on the appropriateness of radiological criteria used for diagnosing lymph node metastases. Size of nodes and evidence of necrosis are still the most important radiological criteria. However, the size shows great variability. A spherical lymph node larger than 10mm is an indicator for a malignant node, whereas an oval shape and/or a fatty hilus are more benign signs. But there are many limitations and different cut offs published in the literature, indicating that the size of a lymph node is not a reliable criteria for the assessment of lymph nodes in the head and neck region. Today new high-resolution MRI sequences and the development of specific contrast agents are offering new possibilities in the diagnostic work-up of head and neck lymph nodes. Ultrasmall superparamagnetic iron oxide particles (USPIOs) are resulting after intravenous application in a reduction of the T2 relaxation time. This is causing a signal decrease on T2-weighted MR images in benign lymph nodes after administration of USPIOs, whereas malignant lymph nodes do not show a significant signal decrease. Some clinical studies presented already very promising results. Based on the fact, that the size evaluation of lymph nodes in the head and neck has not changed during the last decade, this paper will mainly focus on MRI with new contrast agents and new techniques as diffusion weighted imaging (DWI).

Dynamic contrast-enhanced CT of head and neck tumors: perfusion measurements using a distributed-parameter tracer kinetic model. Initial results and comparison with deconvolution-based analysis

The objective of this work was to evaluate the feasibility of a two-compartment distributed-parameter (DP) tracer kinetic model to generate functional images of several physiologic parameters from dynamic contrast-enhanced CT data obtained of patients with extracranial head and neck tumors and to compare the DP functional images to those obtained by deconvolution-based DCE-CT data analysis. We performed post-processing of DCE-CT studies, obtained from 15 patients with benign and malignant head and neck cancer. We introduced a DP model of the impulse residue function for a capillary-tissue exchange unit, which accounts for the processes of convective transport and capillary-tissue exchange. The calculated parametric maps represented blood flow (F), intravascular blood volume (v(1)), extravascular extracellular blood volume (v(2)), vascular transit time (t(1)), permeability-surface area product (PS), transfer ratios k(12) and k(21), and the fraction of extracted tracer (E). Based on the same regions of interest (ROI) analysis, we calculated the tumor blood flow (BF), blood volume (BV) and mean transit time (MTT) by using a modified deconvolution-based analysis taking into account the extravasation of the contrast agent for PS imaging. We compared the corresponding values by using Bland-Altman plot analysis. We outlined 73 ROIs including tumor sites, lymph nodes and normal tissue. The Bland-Altman plot analysis revealed that the two methods showed an accepted degree of agreement for blood flow, and, thus, can be used interchangeably for measuring this parameter. Slightly worse agreement was observed between v(1) in the DP model and BV but even here the two tracer kinetic analyses can be used interchangeably. Under consideration of whether both techniques may be used interchangeably was the case of t(1) and MTT, as well as for measurements of the PS values. The application of the proposed DP model is feasible in the clinical routine and it can be used interchangeably for measuring blood flow and vascular volume with the commercially available reference standard of the deconvolution-based approach. The lack of substantial agreement between the measurements of vascular transit time and permeability-surface area product may be attributed to the different tracer kinetic principles employed by both models and the detailed capillary tissue exchange physiological modeling of the DP technique.

In vivo proton MR spectroscopy of primary tumours, nodal and recurrent disease of the extracranial head and neck

Benign and malignant neoplasms as well as metastatic lymph nodes of 39 patients were examined using localized single voxel magnetic resonance spectroscopy (MRS) [repetition time (TR)xa01500, echo time (TE)xa0135) at 1.5xa0T. New techniques with simultaneous correction of motion artefacts during the acquisition, three-dimensional saturation pulses, respiratory triggering and smaller volume of interest (VOI) size, were applied. Ratios of peak areas under the choline (Cho) and creatine (Cr) resonances were estimated in all cases and compared with those from samples of normal tissue. Ninety one spectra were acquired in 39 patients, 63 of which were suitable for further evaluation. The smallest VOI was 0.40xa0cm3. The Cho/Cr ratios in all malignant neoplasms (mean: 5.2, range: 1.7–17.8) were significantly elevated relative to those in the normal muscle structures (mean: 0.9, range: 0.2–1.4), while those in the benign neoplasms were elevated (mean: 24.4, range: 1.4–59.7) with respect to those in the malignant ones. The average Cho/Cr ratio in the metastatic lymph nodes was significantly higher (mean: 4.8, range: 3.3–5.6) than that for benign lymphoid hyperplasia (mean: 2.2, range: 1.0–3.0). MRS measurements were able to differentiate recurrent disease from post-therapeutic tissue changes in 11 out of 13 patients.

Functional CT of squamous cell carcinoma in the head and neck: repeatability of tumor and muscle quantitative measurements, inter- and intra-observer agreement

Our purpose was to determine the repeatability of squamous cell cancer in head and neck (SCCHN) and muscle tissue vascularity measurements as well as the inter- and intra-observer agreement using dynamic contrast-enhanced (DCE) multi-detector CT (MDCT). Twelve patients with histologically proven SCCHN were twice examined within 46xa0h. Measurement error and repeatability were assessed for each of the four functional parameters using the Bland-Altman plots. Two independent observers recorded the vascularity values of the tumor tissue; inter- and intra-observer agreement was assessed using the Bland-Altman plot analysis and intraclass correlation coefficients. For the tumor, the mean difference (95% limits of agreement) was 0.40xa0ml/min/100xa0g tissue (−6.80, 9.60); 0.01 (−0.96, 0.97) ml/100xa0g tissue; 0.20 (−1.80, 2.30) s; and 0.40 (−2.00, 2.80) ml/min/100xa0g tissue for BF, BV, MTT, and PS, respectively. For the muscle, the mean difference (95% limits of agreement) was −0.18 (−1.70, 1.35), 0.04 (−1.17, 1.35), −0.10 (−5.80, 5.60), and −0.10 (−2.20, 2.00), respectively. Measurement changes of at least ±8%, 30%, 36%, and 13% were found to be significant for BF, BV, MTT, and PS, respectively. There was better intra- than inter-observer agreement.

Usefulness of MRI volumetric evaluation in patients with squamous cell cancer of the head and neck treated with neoadjuvant chemotherapy

The purpose was to evaluate the efficacy of tumor volumetry on MRI as predictive of response to treatment with induction chemotherapy, comparing the results with endoscopy.

Dynamic contrast-enhanced CT of head and neck tumors: comparison of first-pass and permeability perfusion measurements using two different commercially available tracer kinetics models.

RATIONALE AND OBJECTIVESnTo evaluate the interchangeability of perfusion parameters between two software packages for the postprocessing of dynamic contrast-enhanced (DCE) computed tomographic images of head and neck tumors.nnnMATERIALS AND METHODSnDCE computed tomographic images of 75 patients with head and neck tumors were postprocessed using a software package based on the maximum-slope approach and Patlak analysis, as well as a software package with deconvolution-based analysis incorporating an adiabatic approximation of tissue homogeneity (ATH) model. The evaluated perfusion parameters included blood flow (F), blood volume (v), and permeability-surface area product (PS). Region-of-interest (ROI) analysis of the tumors and the metastatic lymph nodes was performed. The perfusion parameters were compared using the Wilcoxon matched-pairs test and Bland-Altman plots.nnnRESULTSnOne hundred fifty-two ROIs of tumors and nodes were outlined and analyzed. Moderate to good correlations were demonstrated between the various perfusion values (r = 0.56-0.72, P < .0001). The Wilcoxon test revealed a significant difference between the two methods (P < .001), with the F, v, and PS values obtained using the maximum-slope approach and Patlak analysis higher than those obtained using deconvolution-based analysis with the assumptions of the ATH model. The Bland-Altman plots for F and v values revealed a proportionality trend with outliers, which were strongly associated with the magnitudes of the parameters. Analysis of the PS values did not show any systematic bias.nnnCONCLUSIONnThere were significant differences in the perfusion parameters obtained using the two software packages, and thus, these parameters are not directly interchangeable.

Computed Tomography Assessment of Cerebral Perfusion Using a Distributed Parameter Tracer Kinetics Model: Validation with H2(15)O Positron Emission Tomography Measurements and Initial Clinical Experience in Patients with Acute Stroke

We describe a distributed parameter (DP) model for tracer kinetic analysis in brain and validate the derived perfusion values with positron emission tomography (PET) scans. The proposed model is applied on actual clinical cases of hemispheric stroke. Nine patients with experienced transient ischaemic attack or minor stroke and a stenosis of the internal carotid artery were referred for computed tomography (CT) and PET imaging. The applicability of the DP model in clinical practice was tested in seven patients with acute stroke who received a baseline perfusion CT study and a noncontrast follow-up CT study after 2.4 ± 1.8 days. The mean blood flow (F) value for all patients with carotid stenosis in the pooled data (54 regions of interest (ROIs)) was 37.9 ± 11.2 mL/min per 100 g in perfusion CT and 35.6 ± 9.8 mL/min per 100 g in perfusion PET imaging [r = 0.77 (P = 0.00)]. Regression analysis of the pooled ROIs for every patient revealed significant correlation between F values in seven patients [r = 0.50 to 0.79 (r2-values ranged from 0.45 to 0.79), (0.01 ≤P ≤ 0.05)]. Parametric maps that corresponded to all physiologic parameters were generated for every perfusion CT in the patients with acute stroke using the DP model. The ischaemic area was better delineated in F, intravascular blood volume and lag time (tlag) maps. The correlation coefficient comparing the visually outlined regions of abnormality between the tlag parametric map and the follow-up CT scans was 0.81 (P = 0.003). In conclusion, DP physiological model using more realistic pharmacokinetics is feasible in dynamic contrast-enhanced CT of the brain in patients with acute and chronic cerebrovascular disease.

Primary B cell lymphoma of the sphenoid sinus: CT and MRI characteristics with correlation to perfusion and spectroscopic imaging features

Primary non-Hodgkin lymphoma (NHL) of the paranasal sinuses is a rare neoplasm that cannot be easily diagnosed and differentiated as its clinical, histological, and imaging features are similar to those of other inflammatory and tumorous diseases in their early stages. We evaluated the morphological and functional imaging characteristics of primary NHL of the sphenoid sinus using CT and MR imaging. Morphological CT and MR imaging as well as perfusion CT imaging and proton MR spectroscopy (PRESS technique, TExa0=xa0135) was performed in three patients with the histological diagnosis of highly malignant primary B cell lymphoma of the sphenoid sinus. In all patients an inhomogeneous contrast agent enhancement as well as bony erosion of the sphenoid sinus was identified in CT and MR sections. In one patient an infiltration of the adjacent dura was present. The mean blood flow of the lymphomas was 135xa0ml/min per 100xa0g tissue, the mean blood volume was 8.06xa0ml/min, while the mean transit time and the mean permeability surface area product values were 5.11xa0s and 26.53xa0ml/min per 100xa0g, respectively. The mean choline to creatine ratio in the proton MR spectroscopy was 5.7. Cross-sectional imaging findings are not sufficient to establish the diagnosis of a primary NHL in the sphenoid sinus. Physiologic imaging offers valuable information that may be characteristic of the tumor. Future studies may lead to a safe differentiation of the lymphomas from other pathologic entities based on the combination of morphological and functional imaging.

Cetuximab enhances the efficacy of bortezomib in squamous cell carcinoma cell lines

PurposeProteasome inhibition has been shown to be effective in multiple myeloma and solid tumor models. In this in vitro study, we investigated the antitumor effect of bortezomib (Velcade®) in combination with cetuximab in squamous cell carcinoma cell lines (SCC).MethodsDose-escalation studies were performed in five squamous cell carcinoma cell lines using bortezomib or cetuximab alone or in combination. Cell survival and growth inhibition were measured quantitatively using an MTT and LDH assay.ResultsBortezomib alone showed a significant antiproliferative activity in all SCC cell lines (Pxa0<xa00.042), and the activity was further significantly enhanced by the addition of cetuximab (Pxa0<xa00.043).ConclusionsOur results indicate that cetuximab increases the cytotoxic activity of bortezomib in SCC cell lines. Combination therapy of SCC with bortezomib and cetuximab might be less toxic than conventional drug regimens used in the treatment of these tumors.

Nucleolysis in the herniated disk

ZusammenfassungIn Deutschland wie in anderen Industrieländern stellen der Diskusprolaps und die damit verbundene Schmerzsymptomatik ein bedeutsames und zunehmendes Gesundheitsproblem dar. Wenn die Möglichkeiten der konservativen Therapie ausgeschöpft sind, ist die Nukleolyse als minimalinvasive Alternative zur Operation zu diskutieren. Hierbei werden unter CT-Steuerung chondrolytische oder quelldruckmindernde Substanzen in den Nucleus pulposus einer protrudierten Bandscheibe injiziert. Unter den zahlreichen Substanzen, die bisher zum Einsatz kamen, erwies sich v.xa0a. die Nukleolyse mit einem Ozon-Sauerstoff-Gemisch als viel versprechend. Neben seiner hohen Wasserbindungskapazität vermag Ozon die Schmerzmediatoren vor Ort über mehrere Monate zu hemmen, wirkt antiinflammatorisch und durchblutungsfördernd. Ozon wandelt sich im Körper in reinen Sauerstoff um und besitzt eine geringe Allergenität. Bei der Nukleolyse handelt es sich um das älteste minimalinvasive Verfahren zur Therapie eines Bandscheibenvorfalls. Vergleichende Studien konnten eine Überlegenheit neuerer Therapiekonzepte, z.xa0B. der perkutanen Nukleotomie oder der Laserbehandlung, nicht bestätigen.AbstractBack pain associated with a herniated disk has become an important and increasing general health problem in Germany and other industrialized countries. After all methods of conservative treatment have been exhausted, nucleolysis may be a minimally invasive alternative to surgery. In nucleolysis, chondrolytic substances or other substances, which reduce the pressure within the disk by other means, are injected into the nucleus pulposus under CT guidance. Among various substances, which have been employed for nucleolysis, an ozone-oxygen mixture appears to be very promising. The water-binding capacity of ozone results in a reduction of pain for several months. Moreover, it has an anti-inflammatory effect and results in an increase of perfusion. Ozone is converted into pure oxygen in the body and has a low allergic potential. Recent minimally invasive therapeutic methods such as percutaneous nucleotomy or laser treatment do not result in superior results compared with nucleolysis.