MRI diffusion phantoms: ADC and relaxometric measurement comparisons between polyacrylamide and agarose gels.

PURPOSE: The aim of this study is to compare polyacrylamide and agarose gels, as components of a simple MRI phantom, for the measurements of Apparent Diffusion Coefficient (ADC), T1 and T2 relaxation times. MATERIALS AND METHODS: Five (5) test tubes with polyacrylamide gels of different monomer concentrations and six (6) test tubes of different agarose gel concentrations were used as a phantom for ADC, T1 and T2 measurements, which were expressed as 2D color parametric maps, on a 1.5 T clinical MRI system. ADC and T2 maps were calculated utilizing a Weighted Linear (WL) regression fitting algorithm. T1 maps were calculated utilizing a standard non-linear fitting algorithm. RESULTS: In agarose gels, ADC measurements are independent of the agarose concentration, whereas the T1 and T2 relaxation times decrease with increasing agarose concentration. On the contrary, in polyacrylamide gels, ADC measurements decrease quadratically while increasing the monomer concentration, whereas the T1 and T2 relaxation times reveal a linear decrease with increasing monomer concentration. CONCLUSION: Polyacrylamide gels can serve as a better means for simulating ADC values, as compared with the agarose gels used in this study.

Dosimetric performance of the Elekta Unity MR-linac system: 2D and 3D dosimetry in anthropomorphic inhomogeneous geometry.

Following the clinical introduction of the Elekta Unity MR-linac, there is an urgent need for development of dosimetry protocols and tools, not affected by the presence of a magnetic field. This work presents a benchmarking methodology comprising 2D/3D passive dosimetry and involving on-couch adaptive treatment planning, a unique step in MR-linac workflows. Two identical commercially available 3D-printed head phantoms (featuring realistic bone anatomy and MR/CT contrast) were employed. One phantom incorporated a film dosimetry insert, while the second was filled with polymer gel. Gel dose-response characteristics were evaluated under the Unity irradiation and read-out conditions, using vials and a cubic container filled with gel from the same batch. Treatment plan for the head phantoms involved a hypothetical large C-shape brain lesion, partly surrounding the brainstem. An IMRT step-and-shoot 7-beam plan was employed. Pre-treatment on-couch MR-images were acquired in order for the treatment planning system to calculate the virtual couch shifts and perform adaptive planning. Absolute 2D and relative 3D measurements were compared against calculations related to both adapted and original plans. Real-time dose accumulation monitoring in the gel-filled phantom was also performed. Results from the vials and cubic container suggest that gel dose-response is linear in the dose range investigated and signal integrity is mature at the read-out timings considered. Head phantom 2D and 3D measurements agreed well with calculations with 3D gamma index passing rates above 90% in all cases, even with the most stringent criteria used (2 mm/2%). By exploiting the 3D information provided by the gel, comparison also involved DVHs, dose-volume and plan quality metrics, which also reflected the agreement between adapted and delivered plans within ±4%. No considerable discrepancies were detected between adapted and original plans. A novel methodology was developed and implemented, suitable for QA procedures in Unity. TPS calculations were validated within the experimental uncertainties involved.

Critical transitions in suspended sediment dynamics in a temperate meso-tidal estuary.

There is growing consensus that human interventions can fundamentally change fine sediment transport in estuaries. Critical transitions in response to human interventions have been hypothesized based on indirect observational evidence and theoretical understanding. So far direct evidence has been lacking. Based on a 20 year data-set of surface suspended particulate matter (SPM) concentrations, we present empirical evidence of critical transitions in a temperate meso-tidal estuary. In 2008-2009 the SPM dynamics of the Scheldt estuary (Belgium/The Netherlands) changed dramatically. Not only did the total amount of sediment in suspension increase, a new maximum turbidity zone (MTZ) at typical winter discharges appeared. At intermediate and low summer discharges the longitudinal distribution of SPM now flickers between two markedly different states. Our data suggest that a range of human interventions (fairway widening and deepening, dredging and dumping activities) set the scene leading to the observed transitions. Moreover the freshwater MTZ in the Scheldt and in its major tributary exhibit an increasing sensitivity towards freshwater discharge, coinciding with water quality improvements. This suggests large scale impacts of changes in eutrophication status on estuarine sediment dynamics. This has largely been a blind spot in morphodynamic research.

Characterization of a novel 3D printed patient specific phantom for quality assurance in cranial stereotactic radiosurgery applications.

In single-isocenter stereotactic radiosurgery/radiotherapy (SRS/SRT) intracranial applications, multiple targets are being treated concurrently, often involving non-coplanar arcs, small photon beams and steep dose gradients. In search for more rigorous quality assurance protocols, this work presents and evaluates a novel methodology for patient-specific pre-treatment plan verification, utilizing 3D printing technology. In a patient's planning CT scan, the external contour and bone structures were segmented and 3D-printed using high-density bone-mimicking material. The resulting head phantom was filled with water while a film dosimetry insert was incorporated. Patient and phantom CT image series were fused and inspected for anatomical coherence. HUs and corresponding densities were compared in several anatomical regions within the head. Furthermore, the level of patient-to-phantom dosimetric equivalence was evaluated both computationally and experimentally. A single-isocenter multi-focal SRS treatment plan was prepared, while dose distributions were calculated on both CT image series, using identical calculation parameters. Phantom- and patient-derived dose distributions were compared in terms of isolines, DVHs, dose-volume metrics and 3D gamma index (GI) analysis. The phantom was treated as if the real patient and film measurements were compared against the patient-derived calculated dose distribution. Visual inspection of the fused CT images suggests excellent geometric similarity between phantom and patient, also confirmed using similarity indices. HUs and densities agreed within one standard deviation except for the skin (modeled as 'bone') and sinuses (water-filled). GI comparison between the calculated distributions resulted in passing rates better than 97% (1%/1 mm). DVHs and dose-volume metrics were also in satisfying agreement. In addition to serving as a feasibility proof-of-concept, experimental absolute film dosimetry verified the computational study results. GI passing rates were above 90%. Results of this work suggest that employing the presented methodology, patient-equivalent phantoms (except for the skin and sinuses areas) can be produced, enabling literally patient-specific pre-treatment plan verification in intracranial applications.

The impact of spin coupling signal loss on fat content characterization in multi-echo acquisitions with different echo spacing.

PURPOSE: This study aimed to assess the effect of echo spacing in transverse magnetization (T2) signal decay of gel and fat (oil) samples. Additionally, we assess the feasibility of using spin coupling as a determinant of fat content. METHODS: Phantoms of known T2 values, as well as vegetable oil phantoms, were scanned at 1.5T scanner with a multi echo FSE sequence of variable echo spacing above and below the empirical threshold of 20ms for echo train signal modulation (6.7, 13.6, 26.8, and 40ms). T2 values were calculated from monoexponential fitting of the data. Relative signal loss between the four acquisitions of different echo spacing was calculated. RESULTS: Agreement in the T2 values of water gel phantom was observed in all acquisitions as opposed to fat phantom (oil) samples. Relative differences in signal intensity between two successive sequences of different echo spacing on composite fat/water regions of interest was found to be linearly correlated to fat fraction of the ROI. CONCLUSION: The sample specific degree of signal loss that was observed between different fat samples (vegetable oils) can be attributed to the composition of each sample in J coupled fat components. Hence, spin coupling may be used as a determinant of fat content.

Factors predicting a positive capsule endoscopy in past overt obscure gastrointestinal bleeding: a multicenter retrospective study.

OBJECTIVES: Capsule endoscopy (CE) remains the examination of choice for the investigation of obscure gastrointestinal bleeding. Although the factors predicting positive CE findings in the overall obscure gastrointestinal bleeding have been investigated, the clinical characteristics that predict a positive CE in patients with past overt obscure gastrointestinal bleeding (OOGIB) have not been systematically studied. METHODS: Between September 2004 and December 2013, 262 patients underwent CE for evaluation of past OOGIB after negative upper and lower endoscopy, and other diagnostic modalities. Patients' records were retrospectively reviewed to assess the factors that could possibly predict positive CE findings. RESULTS: Two hundred and twenty four patients with a median age of 70 years (range: 17-87) were enrolled in the final analysis and were divided into two groups; those who had positive (group A: 118 patients) and those who had negative CE findings (group B: 106 patients). The overall diagnostic yield of CE was 52.68 %. Multivariate analysis demonstrated that age >65 years, anticoagulant use, antiplatelet use, and non-steroidal anti-inflammatory drugs use were independent predictive factors for positive findings on CE. Of the 118 patients with positive CE, therapeutic interventions were performed in 56 patients (47.46 %). Recurrence of bleeding presented in nine patients of group B compared with 39 patients of group A (p <0.001). CONCLUSIONS: Certain clinical characteristics predict a positive CE in patients with past OOGIB. Patients with OOGIB and negative CE had a considerably lower rebleeding rate, and further invasive investigational procedures may be adjourned or may not be required, though such recommendation warrants further validation. Hippokratia 2016, 20(2): 127-132.

Occupational Electromagnetic Fields exposure in Magnetic Resonance Imaging systems - Preliminary results for the RF harmonic content.

PURPOSE: European legislation concerning the protection of workers from exposure to Electromagnetic Fields (EMF) was recently (26.6.2013) completed by Directive 2013/35/ΕU. This Directive is a specific one of the framework Directive 89/391/EEC and part of the overall legislation for Occupational Health and Safety (OHS). Magnetic Resonance Imaging (MRI) systems have played a key role, both in the postponement of the former 2004/40 EMF Directive and in the formation of the latest limits adopted by the new Directive. On the other hand, MRI systems are associated with the exposure of personnel to EMF of various frequencies and modulations, arousing peculiar safety issues. Therefore, we will try to acquire the highly important knowledge of the exact occupational exposure levels, in all working scenarios and practices. METHODS: Different MRI systems (1.5 and 3 T) have been chosen for a variety of measurements in order to assess occupational exposure compared to the limits (ALs) of the Directive and to the main OHS principles. Gradient function of MRI systems results in low frequency exposure, while high frequency exposure comes from the application of the RF excitation frequency. RESULTS: In most of the cases the RMS and peak value measurements do not exceed the corresponding ALs, apart from a few specific hot spots, manageable through OHS principles. DISCUSSION: Complete occupational exposure results can form the basis for dealing with multiple exposures present in MRI systems. Peculiar RF harmonic components, of no safety concern, were detected. Their origin is under examination.

Hemodynamic evidence linking cognitive deficits in clinically isolated syndrome to regional brain inflammation.

BACKGROUND AND PURPOSE: To investigate the relation between hemodynamic measurements and memory function in patients with clinically isolated syndrome (CIS). METHODS: Forty CIS patients were administered tests of verbal short-term/working memory and passage learning. Using dynamic susceptibility contrast MRI cerebral blood volume (CBV), cerebral blood flow and mean transit time values were estimated in 20 cerebral regions of interest, placed in normal appearing white matter (NAWM) and normal appearing deep gray matter structures, bilaterally. RESULTS: CIS patients showed significantly impaired scores on working memory and secondary verbal memory that correlated inversely with elevated CBV values in the left frontal and periventricular NAWM, thalamus, right caudate and corpus callosum. CONCLUSIONS: Verbal memory in CIS correlates inversely with elevated CBV values of brain structures involved in memory. As these hemodynamic changes, detected in CIS, are indicative of inflammation, the observed cognitive disturbances may relate to widespread brain inflammatory processes that prevail in early multiple sclerosis.

Can capsule endoscopy be used as a diagnostic tool in the evaluation of nonbleeding indications in daily clinical practice? A prospective study.

OBJECTIVE: To evaluate the diagnostic yield of capsule endoscopy (CE) and its impact on treatment and outcome in patients without bleeding indications. SUBJECTS AND METHODS: One hundred and sixty-five nonbleeding patients were enrolled in the study. The most common indications for CE were chronic abdominal pain alone (33 patients) or combined with chronic diarrhea (31 patients) and chronic diarrhea alone (30 patients). Among the 165 patients, 129 underwent CE for evaluation of gastrointestinal symptoms and 36 for surveillance or disease staging. RESULTS: CE findings were positive, suspicious and negative in 73 (44.2%), 13 (7.9%) and 79 (47.9%) of cases, respectively. The diagnostic yield was highest in patients with refractory celiac disease (10/10, 100%) and suspected Crohn's disease (5/6, 83.3%), followed by patients with chronic abdominal pain and chronic diarrhea (13/31, 41.9%), established Crohn's disease (2/6, 33.3%), chronic diarrhea alone (8/30, 26.7%), chronic abdominal pain alone (8/33, 24.2%) and other indications (3/13, 23.1%) (p < 0.005). The CE findings led to a change of medication in 74 (47.7%) patients, surgery in 15 (9.7%), administration of a strict gluten-free or other special diet in 13 (8.4%) and had other consequences in 11 (6.7%). Management was not modified in 42 (27.1%) patients. Among symptomatic patients (n = 129), 29 (22.5%) were lost to follow-up. The remaining 100 patients were followed up for 8.7 ± 4.0 months (range 2-19). Among the latter, resolution or improvement of symptoms was observed in 86 (86%) patients, no change in 11 (11%) and 3 (3%) died. All 86 patients who experienced resolution or improvement of their symptoms had a modification of their management after CE; only 7/11 patients whose symptoms did not change (63.6%) and 2/3 patients who died (66.7%) had a modification of management (p < 0.001). CONCLUSIONS: CE appears to be a useful tool in the evaluation of patients with nonbleeding indications. The outcome of most patients with negative findings was excellent.

Technical note: a fast laser-based optical-CT scanner for three-dimensional radiation dosimetry.

PURPOSE: To introduce a novel laser-based optical-CT scanner for the readout of three-dimensional (3D) radiation dosimeters. METHODS: The scanner employs a diode laser, a cylindrical lens, a motorized linear rail, a rotation stage, and a charge-coupled device camera. The scanner operates in a translate-rotate fashion and may be set up in two configurations depending on the orientation of the cylindrical lens. The attenuation coefficient versus dose response was determined for a normoxic N-vinylpyrrolidone based polymer gel dosimeter. Cylindrical dosimeters, 2 cm diameter, were homogenously irradiated to known doses up to 60 Gy using a 6 MV linear accelerator. For a test irradiation, a 5 cm diameter dosimeter was irradiated along its cylindrical axis using a rectangular 1 cm x 1 cm irradiation beam. The dose readout of this scanner was compared to the corresponding readout of a common wide illumination and area detector optical-CT scanner. RESULTS: The attenuation coefficient versus dose response of the laser-based system was found to be linear up to 60 Gy (r2 = 0.997) compared to the wide field illumination based optical-CT scanner, which exhibits linearity up to 32 Gy (r2 = 0.996). The noise in the reconstructed attenuation coefficient maps was +/- 7.2 x 10(-2) mm(-1) versus +/- 9.5 x 10(-3) mm(-1) for the laser-based system and the wide field illumination system, respectively. CONCLUSIONS: We have developed a novel laser-based optical-CT scanner, which is capable of generating fast 3D dosimetric data using a scattering polymer gel dosimeter. Our data demonstrate that the dose readout of this scanner preserves the advantage of existing laser-based optical-CT scanners in providing measurements, which are minimally affected by scattered light. For accurate reconstruction of the attenuation coefficients, noise reduction techniques need to be applied.

Benign multiple sclerosis in Crete.

Our objective was to study multiple sclerosis on Crete, an island of 0.6 million inhabitants sharing a similar genetic background and the same environment. Case ascertainment was achieved using the MS Epidemiology Program Project of Crete. The diagnosis and classification of multiple sclerosis were made by established clinical and magnetic resonance imaging criteria, and disease evolution was assessed by periodic evaluations. Thorough clinical and laboratory evaluations were conducted; a detailed history, including a questionnaire of 36 items, was taken. Data obtained were analysed for possible interaction with disease prognosis. We identified 587 cases of multiple sclerosis (F:M = 1.6), >90% of which were of Cretan origin from both parental lines. Age at onset was 31.5 +/- 10.3 years (mean +/- SD) and disease duration 12.7 +/- 9.1 years. About 84.6% had relapsing remitting multiple sclerosis, 9.4% primary progressive multiple sclerosis and 6% clinically isolated syndrome. Nearly 40% of our multiple sclerosis patients with disease duration >10 years (mean = 16.2 +/- 5.3 years) remained with no or mild disability (Expanded Disability Status Scale [EDSS] < or =3). Also, about 30% of patients with relapsing remitting multiple sclerosis showed benign disease evolution (EDSS < or =3) more than 20 years (mean = 24.0 +/- 3.3) after onset. Factors predisposing to benign multiple sclerosis included younger age at onset, shorter disease duration and a lower number of relapses. We conclude that a substantial proportion of patients with multiple sclerosis from Crete follow a rather benign disease course, and this may relate to the genetic background of the population and/or to environmental factors.

Small SRS photon field profile dosimetry performed using a PinPoint air ion chamber, a diamond detector, a novel silicon-diode array (DOSI), and polymer gel dosimetry. Analysis and intercomparison.

Small photon fields are increasingly used in modern radiotherapy and especially in IMRT and SRS/SRT treatments. The uncertainties related to small field profile measurements can introduce significant systematic errors to the overall treatment process. These measurements are challenging mainly due to the absence of charged particle equilibrium conditions, detector size and composition effects, and positioning problems. In this work four different dosimetric methods have been used to measure the profiles of three small 6 MV circular fields having diameters of 7.5, 15.0, and 30.0 mm: a small sensitive volume air ion chamber, a diamond detector, a novel silicon-diode array (DOSI), and vinyl-pyrrolidone based polymer gel dosimeter. The results of this work support the validity of previous findings, suggesting that (a) air ion chambers are not suitable for small field dosimetry since they result in penumbra broadening and require significant corrections due to severe charged particle transport alterations; (b) diamond detectors provide high resolution and rather accurate small field profile measurements, as long as positioning problems can be addressed and the necessary dose rate corrections are correctly applied; and (c) the novel silicon-diode array (DOSI) used in this study seems to be adequate for small field profile measurements overcoming positioning problems. Polymer gel data were assumed as reference data to which the other measurement data were compared both qualitatively and quantitatively using the gamma-index concept. Polymer gels are both phantom and dosimeter, hence there are no beam perturbation effects. In addition, polymer gels are tissue equivalent and can provide high-spatial density and high-spatial resolution measurements without positioning problems, which makes them useful for small field dosimetry measurements. This work emphasizes the need to perform beam profile measurements of small fields (for acceptance, commissioning, treatment planning systems data feed, and periodic quality assurance purposes) using more than one dosimetric method. The authors believe this to be a safe way towards the reduction of the overall uncertainty related to SRS/SRT treatments.

A short course of preoperative radiotherapy improves prognosis of operable rectal carcinoma: a case control study.

BACKGROUND/AIMS: Randomized Swedish studies demonstrate the efficacy of a 5-fraction course of preoperative radiotherapy for rectal carcinoma. The present study evaluates the results in a single Greek institution over a 10-year period, with a similar regimen. METHODOLOGY: During the period of 1995-2000, 150 consecutive patients with Dukes' B or C rectal cancer were matched to receive preoperative radiotherapy (Group I) or not (Group II). Seventy-five patients received pelvic radiotherapy of 2500cGY/5 fractions, followed by surgery within one week. Radiotherapy was delivered through 4 portals, with the patient lying in the prone position. A CT scan was used to define treatment volume. The 5-fraction course was used for lesions that seemed readily resectable. Patients in both groups received adjuvant chemotherapy. Local recurrence, disease-free interval and 5-year survival were evaluated and analyzed. RESULTS: The disease-free interval was significantly longer in Group I (p < 0.0005). This benefit was mainly due to a significantly lower incidence of local recurrence in Group I (9/75, 12%) compared with Group II (30/75, 40%) (p < 0.0005). The incidence of distant metastases was not significantly different between the 2 groups. The 5-year survival for all patients, who underwent "curative" surgery was significantly higher in Group I (77.3%) as compared to Group II (39%), (p < 0.0005). CONCLUSIONS: Patients with resectable rectal cancer who received 2500cGy/5 fractions preoperative radiotherapy to the pelvis had excellent local control of disease, longer disease-free interval and higher 5-year survival than patients who did not. These patients were able to undergo sphincter preserving surgery and adjuvant chemotherapy.

An evaluation of the dosimetric performance characteristics of N-vinylpyrrolidone-based polymer gels.

The aim of this work was to investigate the dosimetric performance properties of the N-vinylpyrrolidone argon (VIPAR) based polymer gel as a dosimetric tool in clinical radiotherapy. VIPAR gels with a larger concentration of gelatin than the standard recipe were manufactured and irradiated up to 68 Gy using a 6 and 18 MV linear accelerator. Using MRI, the R2-dose response was recorded at different imaging sessions within a 34 day time period post-irradiation. The R2-dose response was found to be linear between 5 and 68 Gy. Although dose sensitivity did not show significant variation with time, the measured R2-dose values showed an increasing trend, which was less evident beyond 17 days. At one day post-irradiation, calculated dose standard uncertainties at 20 Gy and 56 Gy were 2.2% and 1.7%, providing a dose resolution of 0.45 Gy and 0.97 Gy, respectively. Although these values fulfilled the 2% limit of ICRU, when gels were imaged at one day post-irradiation, it was shown that the temporal evolution of the R2 values deteriorated the per cent standard uncertainty and the dose resolution by approximately 57%, when imaged 17 days post-irradiation. Variation in the coagulation temperature of the gels did not impact the R2-dose sensitivity. This study has shown that the VIPAR gel has the properties of a dosimetric tool required in clinical radiotherapy, especially in applications where a wide dose dynamic range is employed. For results with the lowest per cent uncertainty and the optimum dose resolution, the dosimetry gels used in this work should be MR scanned at one day post-irradiation. Furthermore, a preliminary study on the R2-dose response of a new normoxic N-vinylpyrrolidone-based polymer gel showed that it could potentially replace the traditional VIPAR gel formulation, while preserving the wide dynamic dose response inherent to that monomer.

In vitro studies on ultrasmall superparamagnetic iron oxide nanoparticles coated with gummic acid for T2 MRI contrast agent.

Ultrasmall superparamagnetic iron oxide nanoparticles coated with gummic acid have been investigated as possible constituents of aqueous ferrofluids for biomedical applications and especially for MRI contrast agent. The structural characteristics and the size of the nanoparticles have been analyzed as well as the magnetic properties. In order to evaluate any possible capabilities as a contrast agent, the relaxation time, T2, of hydrogen protons in the colloidal solutions of nanoparticles have been measured in order to gain information on the relaxation behavior compared to other MRI contrast agents. The in vitro cytotoxicity of the obtained magnetic nanoparticles of iron oxide coated with gummic acid was investigated by two separate methods (MTT and FACS analysis) and by using three different normal and transformed cell lines. Our results showed that the synthesized nanoparticles had no toxic effect on any of the cell lines used.

Experimental determination of the effect of detector size on profile measurements in narrow photon beams.

The aim of this work is to investigate experimentally the detector size effect on narrow beam profile measurements. Polymer gel and magnetic resonance imaging dosimetry was used for this purpose. Profile measurements (Pm(s)) of a 5 mm diameter 6 MV stereotactic beam were performed using polymer gels. Eight measurements of the profile of this narrow beam were performed using correspondingly eight different detector sizes. This was achieved using high spatial resolution (0.25 mm) two-dimensional measurements and eight different signal integration volumes A X A X slice thickness, simulating detectors of different size. "A" ranged from 0.25 to 7.5 mm, representing the detector size. The gel-derived profiles exhibited increased penumbra width with increasing detector size, for sizes >0.5 mm. By extrapolating the gel-derived profiles to zero detector size, the true profile (Pt) of the studied beam was derived. The same polymer gel data were also used to simulate a small-volume ion chamber profile measurement of the same beam, in terms of volume averaging. The comparison between these results and actual corresponding small-volume chamber profile measurements performed in this study, reveal that the penumbra broadening caused by both volume averaging and electron transport alterations (present in actual ion chamber profile measurements) is a lot more intense than that resulted by volume averaging effects alone (present in gel-derived profiles simulating ion chamber profile measurements). Therefore, not only the detector size, but also its composition and tissue equivalency is proved to be an important factor for correct narrow beam profile measurements. Additionally, the convolution kernels related to each detector size and to the air ion chamber were calculated using the corresponding profile measurements (Pm(s)), the gel-derived true profile (Pt), and convolution theory. The response kernels of any desired detector can be derived, allowing the elimination of the errors associated with narrow beam profile measurements.

Relative output factor measurements of a 5 mm diameter radiosurgical photon beam using polymer gel dosimetry.

Besides the fine spatial resolution inherent in polymer gel-magnetic resonance imaging (MRI) dosimetry, the method also features the potential for multiple measurements of varying sensitive volume in a single experiment by integrating results in MRI voxels of finite dimensions (i.e., in plane resolution by slice thickness). This work exploits this feature of polymer gel dosimetry to propose an experimental technique for relative output factor (OF) measurements of small radiosurgical beams. Two gel vials were irradiated with a 5 and 30 mm diameter 6 MV radiosurgery beam and MR scanned with the same slice thickness and three different in plane resolutions. Using this experimental data set, 5 mm OF measurements with the PinPoint ion chamber are simulated by integrating results over a sensitive volume equal to that of the chamber. Results are found in agreement within experimental uncertainties with actual PinPoint measurements verifying the validity of the proposed experimental procedure. The polymer gel data set is subsequently utilized for OF measurements of the 5 mm beam with varying sensitive volume to discuss the magnitude of detector volume averaging effects. Seeking to correct for volume averaging, results are extrapolated to zero sensitive volume yielding a 5 mm OF measurement of (0.66+/-5%). This result compares reasonably with corresponding ionometric and radiographic film measurements of this work and corresponding, limited, data in the literature. Overall, results suggest that polymer gel dosimetry coupled with the proposed experimental procedure helps overcome not only tissue-equivalence and beam perturbation implications but also volume averaging and positioning uncertainties which constitute the main drawback in small radiosurgical beam dosimetry.

A phase I trial of weekly docetaxel and cisplatinum combined to concurrent hyperfractionated radiotherapy for non-small cell lung cancer and squamous cell carcinoma of head and neck.

We conducted a phase I study to evaluate the activity and tolerability of concurrent docetaxel and cisplatinum radiosensitization with hyperfractionated irradiation, in patients with advanced non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN). Nine patients (5 stage III(A) and 4 III(B)) with NSCLC, and 15 with SCCHN (10 stage III and 5 IV) were treated with a b.i.d. hyperfractionated (HF) radiotherapy schedule. The normalized total dose for alpha/beta ratio = 10 Gy was 69.6 Gy for NSCLC and 80.5 Gy for SCCHN patients. The standard dose of cisplatin (10 mg/m(2)) was given combined to docetaxel on a weekly basis. The docetaxel starting dose level was 10 mg/m(2)/week and was escalated by 3 mg/m(2) increments in cohorts of 8 patients (5 SCCHN and 3 NSCLC). DLT (grade 3 malaise) was observed in 4 out of 8 patients treated at the 16 mg/m(2)/week docetaxel dose level. The 13 mg/m(2)/week docetaxel dose level was defined as the MTD causing grade 3 mucositis in 4 out of 8 patients. In total 4 (17%) patients developed grade 3 neutropenia. G-CSF support was given in 1/8, 4/8, and 5/8 patients treated at the 10, 13 and 16 mg/m(2) docetaxel dose levels respectively. Fatigue was the most common adverse event (5/24: 21%) and was responsible for more than 1 week treatment delay in 4 out of 8 patients treated at the 16 mg/m(2)/week docetaxel dose level. Nine (3 NSCLC and 6 SCCHN patients: 37.5%) had treatment delay of 1 week, while 7 (3 NSCLC and 4 SCCHN: 29%) had delays of 2 weeks for combined chemoradiation sequelae. Acute hypersensitivity reactions occurred in 3 (12.5%) patients, and grade 3 mucositis in 2/8, 5/8 and 6/8 patients, treated at 10, 13 and 16 mg/m(2)/week docetaxel dose levels respectively. The overall response rate was 79% (CI = 63-96%) with 33% and 53% CRs for NSCLC and SCCHN patients respectively. There were 3 deaths among 9 NSCLC and 4 among 15 SCCHN patients. Local and/or distant disease recurrences were shown in 4 NSCLC and in 6 SCCHN patients; 5 NSCLC and 9 SCCHN patients are alive with no evidence of tumor progression at 8.5 months mean follow-up time. Radiosensitization with docetaxel and cisplatin given concurrently with HF (b.i.d.) radiotherapy on a weekly basis is a promising approach and the recommended dose for further phase II studies is 10 mg/m(2)/week for both drugs. The antitumor activity shown was significant in both types of tumors. The incorporation of docetaxel in chemoradiotherapy regimens for future treatment of squamous cell carcinoma of the lung and head and neck, merits evaluation in phase II and III trials.

Detection of malignant bone marrow involvement with dynamic contrast-enhanced magnetic resonance imaging.

BACKGROUND: The purpose of this study was to evaluate the role of dynamic contrast-enhanced magnetic resonance imaging (dMRI) in detecting bone marrow involvement in cancer patients. PATIENTS AND METHODS: We studied 50 consecutive patients with histologically confirmed malignant dissemination to the bone marrow, using dMRI of the lumbosacral spine. Time-signal intensity curves were generated from regions of interest (ROIs) obtained from areas of obvious bone marrow disease (group B). In 16 patients from group B with focal disease, ROIs were also placed on areas with apparently normal bone marrow on static magnetic resonance images (group C). Twenty-two patients with no history of malignancy were used as a control group (group A). Wash-in (WIN) and wash-out (WOUT) rates, time to peak (TTPK), time to maximum slope (TMSP) values and WIN/TMSP ratios were calculated for each patient. Mean values for the three groups were compared statistically. Six patients from group B had follow-up dMRI after chemotherapy: four patients achieved a clinical partial response and two had resistant disease. RESULTS: A significant difference was found between groups A and B for all values. Between groups A and C, in spite of the similar static MRI appearance, all values were significantly different. Between groups B and C, a significant difference was found for WIN, WOUT rates and WIN/TMSP ratio. Follow-up dMRI data analysis correlated well with clinical staging. CONCLUSIONS: dMRI can distinguish normal from malignant bone marrow. It may identify malignant bone marrow infiltration in patients with negative static MRI and serve as both a diagnostic and prognostic tool for patients with bone marrow malignancies.

Optimization of a contrast medium suitable for conventional enteroclysis, MR enteroclysis, and virtual MR enteroscopy.

BACKGROUND: The purpose of the current study was to optimize a gadolinium-barium sulfate solution suitable for performing conventional and MR enteroclysis examinations in the same session. METHODS: Eighteen vials of 20% barium sulfate and various gadolinium concentrations (lower 0 ml/lt, higher 45 ml/lt) were prepared and placed in the magnet. The imaging protocol was consisted of the following sequences: true FISP, HASTE with fat saturation and 3d FLASH with fat saturation in various flip angles. Ten patients underwent conventional enteroclysis with 1.2 lt of 20% barium sulfate enema and 18 ml of gadolinium. MR enteroclysis was performed afterwards using true FISP, fat suppressed 3d FLASH and fat suppressed HASTE sequences. RESULTS: The lowest gadolinium concentration in the barium sulfate solution generating low intraluminal signal on HASTE and high intraluminal signal on true FISP and 3d FLASH sequences was 15 ml/lt. The presence of gadolinium did not influence the lumen opacification in conventional enteroclysis examination. In all patients the proposed contrast medium acted as positive in 3d FLASH (T1w), true FISP (T2/T1 w) and as a negative in HASTE (T2w). Bowel wall conspicuity, lumen opacification and distention were ranked as very good to excellent on MR enteroclysis images while artifacts level did not downgraded the overall image quality. High quality virtual MR endoluminal views of the small bowel, based on 3d FLASH images, were obtained in all cases. CONCLUSION: A 20% barium sulfate enema with 15 ml/lt gadolinium is appropriate for conventional and MR enteroclysis examinations.