Age-Related Cortical Thickness Reduction in Non-Demented Down's Syndrome Subjects.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the characteristic pattern of age-related cortical thinning in patients with Down Syndrome (DS), as assessed by MRI and automatic cortical thickness measurements. METHODS: Ninety-one non-demented subjects with DS (range 11-53 years) were examined using a 1.5 T scanner. MRI-based quantification of cortical thickness was performed using FreeSurfer software package., The Pearson product-moment correlation coefficient between age and mean cortical thickness was evaluated for all subjects participating in the study. RESULTS: A significant negative correlation between cortical thickness and age was found bilaterally in the frontal, temporal, parietal and cingulate gyrus. Specific investigation of cerebral lobes showed a more evident involvement of the frontal one, compared to others. Moreover, the age related reduction of cortical thickness appeared to be more significant and rapid in patients between 20 and 30 years of age. CONCLUSIONS: Our findings showed that Down Syndrome subjects are affected by a diffuse cortical thinning. The involvement of cortical structures can be observed at an earlier age than previous studies have reported.

Age effects on cortical thickness in young Down's syndrome subjects: a cross-sectional gender study.

INTRODUCTION: The aim of this study was to determine differences in the characteristic pattern of age-related cortical thinning in men and women with Down's syndrome (DS) by means of MRI and automatic cortical thickness measurements and a cross-sectional design, in a large cohort of young subjects. METHODS: Eighty-four subjects with DS, 30 females (11-35 years, mean age ± SD = 22.8 ± 5.9) and 54 males (11-35 years, mean age ± SD = 21.5 ± 6.5), were examined using a 1.5-T scanner. MRI-based quantification of cortical thickness was performed using FreeSurfer software package. For all subjects participating in the study, the Pearson product-moment correlation coefficient between age and mean cortical thickness values has been evaluated. RESULTS: A significant negative correlation between cortical thickness and age was found in female DS subjects, predominantly in frontal and parietal lobes, bilaterally. In male DS subjects, a significant negative correlation between cortical thickness and age was found in the right fronto-temporal lobes and cingulate regions. Whole brain mean cortical thickness values were significantly negative correlated with age only in female DS subjects. CONCLUSIONS: Females with Down's syndrome showed a strong correlation between cortical thickness and age, already in early age. We suggest that the cognitive impairment due to hormonal deficit in the postmenopausal period could be emphasized by the early structural decline of gray matter in female DS subjects.

Hemodialysis in patients requiring 131I treatment for thyroid carcinoma.

PURPOSE: Thyroid malignancies can be treated by surgery followed by ablation of the remnant tissue with 131I. As iodide removal from the body occurs by renal extraction, in patients suffering from end-stage renal disease it is necessary to properly evaluate both timing and method of the extracorporeal treatment.
 METHODS: We present two patients on regular hemodialysis, admitted in isolation to the Nuclear Medicine Department and treated with 131I for thyroid carcinoma diagnosed during the check-up for transplantation. Both patients underwent two hemodialysis sessions with a portable machine for CRRT (continuous renal replacement therapy), 24 and 48 hours after the administration of 50 mCi of 131I. The nursing staff were monitored with a dosimeter. Radioactivity of the patients, dialysate and urines were measured during hemodialysis. 
 RESULTS: The greater reduction was obtained with the first dialysis, but in both patients a further, though shorter, hemodialysis at 48 hours was necessary for reaching a patient's radioactivity compatible with discharge. Radioactivity measured in the dialysate demonstrated the almost total removal of radioiodine by dialysis alone. In both patients, follow-up exams revealed a complete ablation of thyroid tissue, without signs of local recurrence. The dose of radioactivity of the dialysis staff was below allowable limits. 
 CONCLUSIONS: We conclude that a successful reduction of radioactivity, without dispersing its therapeutic efficacy, can be obtained with daily hemodialysis with a CRRT machine in patients in isolation treated with 131I. A therapeutic model is proposed.

Absorbed dose to lesion and clinical outcome after liver radioembolization with 90Y microspheres: a case report of PET-based dosimetry.

A 54-year-old woman with metastatic colorectal carcinoma underwent liver radioembolization with (90)Y resin microspheres. Microsphere biodistribution was assessed 2 h after the treatment through a 20-min long (90)Y PET scan. Isodose map and lesion dose-volume histogram (DVH) were then evaluated using a MATLAB-based code. Response to therapy was assessed performing a (18)F-FDG PET 6 months after the treatment. At (90)Y PET the patient showed a well-defined horseshoe-shaped hepatic lesion with hot margins and a cold core. The lesion presented a heterogeneous DVH with a hot margin receiving an average radiation dose as high as 287 Gy and a cold area receiving an average radiation dose of 70 Gy approximately. Six months after the treatment the patient reported a complete remission of tumour areas which received a high radiation dose, while progression of metastases was observed in the area that presented scarce microsphere localization at (90)Y PET. According to our experience, the use of (90)Y PET voxel dosimetry may provide a useful tool to assess possible correlations between microsphere biodistribution and clinical outcome of the treatment. In agreement with current literature findings, an average radiation dose greater than approximately 100 Gy may be required to sterilize liver metastases.

Integral dose and radiation-induced secondary malignancies: comparison between stereotactic body radiation therapy and three-dimensional conformal radiotherapy.

The aim of the present paper is to compare the integral dose received by non-tumor tissue (NTID) in stereotactic body radiation therapy (SBRT) with modified LINAC with that received by three-dimensional conformal radiotherapy (3D-CRT), estimating possible correlations between NTID and radiation-induced secondary malignancy risk. Eight patients with intrathoracic lesions were treated with SBRT, 23 Gy × 1 fraction. All patients were then replanned for 3D-CRT, maintaining the same target coverage and applying a dose scheme of 2 Gy × 32 fractions. The dose equivalence between the different treatment modalities was achieved assuming α/ß = 10 Gy for tumor tissue and imposing the same biological effective dose (BED) on the target (BED = 76 Gy(10)). Total NTIDs for both techniques was calculated considering α/ß = 3 Gy for healthy tissue. Excess absolute cancer risk (EAR) was calculated for various organs using a mechanistic model that includes fractionation effects. A paired two-tailed Student t-test was performed to determine statistically significant differences between the data (p ≤ 0.05). Our study indicates that despite the fact that for all patients integral dose is higher for SBRT treatments than 3D-CRT (p = 0.002), secondary cancer risk associated to SBRT patients is significantly smaller than that calculated for 3D-CRT (p = 0.001). This suggests that integral dose is not a good estimator for quantifying cancer induction. Indeed, for the model and parameters used, hypofractionated radiotherapy has the potential for secondary cancer reduction. The development of reliable secondary cancer risk models seems to be a key issue in fractionated radiotherapy. Further assessments of integral doses received with 3D-CRT and other special techniques are also strongly encouraged.

Intensity modulated radiotherapy in early stage Hodgkin lymphoma patients: is it better than three dimensional conformal radiotherapy?

BACKGROUND: Cure rate of early Hodgkin Lymphoma are high and avoidance of late toxicities is of paramount importance. This comparative study aims to assess the normal tissue sparing capability of intensity-modulated radiation therapy (IMRT) versus standard three-dimensional conformal radiotherapy (3D-CRT) in terms of dose-volume parameters and normal tissue complication probability (NTCP) for different organs at risk in supradiaphragmatic Hodgkin Lymphoma (HL) patients. METHODS: Ten HL patients were actually treated with 3D-CRT and all treatments were then re-planned with IMRT. Dose-volume parameters for thyroid, oesophagus, heart, coronary arteries, lung, spinal cord and breast were evaluated. Dose-volume histograms generated by TPS were analyzed to predict the NTCP for the considered organs at risk, according to different endpoints. RESULTS: Regarding dose-volume parameters no statistically significant differences were recorded for heart and origin of coronary arteries. We recorded statistically significant lower V30 with IMRT for oesophagus (6.42 vs 0.33, p = 0.02) and lungs (4.7 vs 0.1 p = 0.014 for the left lung and 2.59 vs 0.1 p = 0.017 for the right lung) and lower V20 for spinal cord (17.8 vs 7.2 p = 0.02). Moreover the maximum dose to the spinal cord was lower with IMRT (30.2 vs 19.9, p <0.001). Higher V10 with IMRT for thyroid (64.8 vs 95, p = 0.0019) and V5 for lungs (30.3 vs 44.8, p = 0.03, for right lung and 28.9 vs 48.1, p = 0.001 for left lung) were found, respectively. Higher V5 and V10 for breasts were found with IMRT (V5: 4.14 vs 20.6, p = 0.018 for left breast and 3.3 vs 17, p = 0.059 for right breast; V10: 2.5 vs 13.6 p = 0.035 for left breast and 1.7 vs 11, p = 0.07 for the right breast.) As for the NTCP, our data point out that IMRT is not always likely to significantly increase the NTCP to OARs. CONCLUSIONS: In HL male patients IMRT seems feasible and accurate while for women HL patients IMRT should be used with caution.

90Y PET-based dosimetry after selective internal radiotherapy treatments.

OBJECTIVES: The decay of 90Y has a minor branch to the O+ first excited state of 89Zr, the de-excitation of which to the fundamental state is followed by a ß+­ß- emission that has been used recently for biodistribution assessment after selective internal radiotherapy (SIRT) treatments. The purpose of the present study is to demonstrate the feasibility of 90Y PET imaging for dose assessment after radioembolization with 90Y microspheres. METHODS: Activity quantification was validated through preliminary phantom studies using a cylindrical body phantom composed of six inserts of different volumes filled with a calibrated amount of 90Y microspheres. A GE Discovery ST PET/CT scanner provided with bismuth germinate (BGO) crystals was used for image acquisition. Images were reconstructed with an ordered subset expectation­maximization method. The effect of object size and the effect of the number of iterations on dose evaluation and volume recovery were investigated. Microsphere dose distribution was then evaluated on one patient (one lesion) who underwent liver SIRT treatment. Dose calculations were made with a MATLAB-based code developed in our department. Dedicated Monte Carlo calculations were executed to evaluate dose S-values for the 90Y source. The activity distribution derived from 90Y PET acquisitions was convolved with the voxel S-values to obtain a three-dimensional absorbed dose distribution and dose­volume histograms. RESULTS: Dosimetry studies carried out on the body phantom with ordered subset expectation­maximization algorithm, three iterations, provided an accuracy of 7.62% in determining the absorbed dose in the largest insert. The dose difference increases as the insert size reduces. Preliminary results on a patient provided a high-resolution absorbed dose distribution map. An average dose of 139.3 Gy was evaluated for the tumor area, with a maximum dose as high as 237.9 Gy. The absorbed dose to the healthy liver was below the tolerance dose of 35 Gy (33.8 Gy). A clear correlation between absorbed dose and tumor response was observed at 18F-fluorodeoxyglucose PET acquired 6 months after treatment. CONCLUSION: According to our experience, 90Y PET is a promising and reliable technique for microsphere dose assessment and might pave the way for a patient-specific PET-based dosimetry after liver SIRT treatments.

Three-dimensional patient-specific dosimetry in radioimmunotherapy with 90Y-ibritumomab-tiuxetan.

Aim of the present article was to perform three-dimensional (3D) single photon emission tomography-based dosimetry in radioimmunotherapy (RIT) with (90)Y-ibritumomab-tiuxetan. A custom MATLAB-based code was used to elaborate 3D images and to compare average 3D doses to lesions and to organs at risk (OARs) with those obtained with planar (2D) dosimetry. Our 3D dosimetry procedure was validated through preliminary phantom studies using a body phantom consisting of a lung insert and six spheres with various sizes. In phantom study, the accuracy of dose determination of our imaging protocol decreased when the object volume decreased below 5 mL, approximately. The poorest results were obtained for the 2.58 mL and 1.30 mL spheres where the dose error evaluated on corrected images with regard to the theoretical dose value was -12.97% and -18.69%, respectively. Our 3D dosimetry protocol was subsequently applied on four patients before RIT with (90)Y-ibritumomab-tiuxetan for a total of 5 lesions and 4 OARs (2 livers, 2 spleens). In patient study, without the implementation of volume recovery technique, tumor absorbed doses calculated with the voxel-based approach were systematically lower than those calculated with the planar protocol, with average underestimation of -39% (range from -13.1% to -62.7%). After volume recovery, dose differences reduce significantly, with average deviation of -14.2% (range from -38.7.4% to +3.4%, 1 overestimation, 4 underestimations). Organ dosimetry in one case overestimated, in the other underestimated the dose delivered to liver and spleen. However, both for 2D and 3D approach, absorbed doses to organs per unit administered activity are comparable with most recent literature findings.

90Y-PET for the assessment of microsphere biodistribution after selective internal radiotherapy.

OBJECTIVES: To demonstrate the feasibility of 90Y-PET imaging for biodistribution assessment after selective internal radiotherapy treatments with 90Y-microspheres, comparing the results with 99mTc-macroaggregated albumin (MAA) images obtained with single-photon emission computed tomography. METHODS: Preliminary studies were performed with the aim of evaluating the imaging system spatial resolution and scanner sensitivity for detecting annihilation photons. Subsequently, microsphere distribution was evaluated in 10 patients who underwent liver selective internal radiotherapy treatment. 99mTc-MAA and 90Y-microsphere were simultaneously injected for immediate monitoring after treatment. For each patient, the metastases detected with 90Y-PET and 99mTc-MAA were assessed and compared with 18F-fluorodeoxyglucose-PET (18F-FDG-PET) obtained before treatment and used as an imaging benchmark procedure. The correlation between these techniques was thus investigated in terms of matching lesions. Lesions were considered true positive in the case of matching with 18F-FDG-PET. The sensitivity of both techniques was evaluated as the true-positive fraction of detected spots in the treated liver sectors. RESULTS: With our experimental setup, a maximum scanner sensitivity of 0.577 and 0.077 cps/MBq was obtained for three-dimensional and two-dimensional acquisitions, respectively. A good correlation was obtained between images obtained before and after treatment, with 90Y-PET being by far the most accurate technique in detecting microsphere distribution and tumor nonhomogeneity areas. A sensitivity as high as 0.91 was obtained with 90Y-PET, whereas 99mTc-MAA imaging showed a SE of 0.75. CONCLUSION: 90Y-PET is a promising and reliable technique for microsphere biodistribution evaluation after liver selective internal radiotherapy treatment. Because of the better resolution and the possibility to perform computed tomography fusion, 90Y-PET images are more accurate than 99mTc-MAA single-photon emission computed tomography, which is now considered the gold standard for biodistribution assessment.

A theoretical dose-escalation study based on biological effective dose in radioimmunotherapy with (90)Y-ibritumomab tiuxetan (Zevalin).

AIM: To investigate the variation in biological effective dose (BED) produced by the uncertainty in absorbed dose and radiobiological parameters in Zevalin radioimmunotherapy. METHODS: Eight patients scheduled for treatment with standard administration of (90)Y-ibritumomab tiuxetan (Zevalin) were studied. Patient-specific pretherapy dosimetry was performed by injection of (111)In-ibritumomab tiuxetan. Absorbed doses and BEDs were calculated for critical organs (COs) and tumours, assuming a 30% dose uncertainty and varying the radiobiological parameters in a reasonable range. In an activity-escalation study, BEDs for the COs were compared with the BED limits of external beam radiotherapy (EBRT) and BEDs for the tumour with the EBRT dose prescriptions. RESULTS: At standard activities, the absorbed doses per unit activity for the COs were in agreement with those in the literature. Absorbed doses to lesions were rather variable, ranging from 1.47 to 16.7 Gy/GBq. Median tumour absorbed dose to lesions in the range 80-110 g was 9.6 Gy/GBq (range 9.2-16.7 Gy/GBq), yielding a mean BED of about 12 Gy for administration of 15 MBq/kg. For the administration of the myeloablative activity of 45 MBq/kg, risk of liver toxicity in one patient would have been foreseen by the model. Considering also the dose uncertainty, the potential risk of liver toxicity in one more patient, lung toxicity in one patient, and kidney toxicity in one patient would have been suggested. The absorbed dose uncertainty was found to be the main source of uncertainty in the BED. As for radiobiological parameters, at myeloablative activities, the increase in the repair half-time for sublethally damaged tissue (T(mu)) from 0.5 h to 5 h induced more consistent increases in mean BED/BED(limit) than alpha/beta variation from 2 Gy to 5 Gy: at 53 MBq/kg, 38% for the liver, and 34% for the lungs and kidneys (about threefold higher than that obtained for the increase alpha/beta). CONCLUSION: At standard activities, absorbed doses to lesions appear to be effective, even though lower than prescribed by EBRT. At myeloablative dosages, the uncertainty associated with the absorbed doses and radiobiological parameters considerably affect BED evaluation and may account for possible "second-organ" toxicities.