Alessandro Carriero

Mesenchymal stromal cell transplantation in amyotrophic lateral sclerosis: a long-term safety study

BACKGROUND AIMS Mesenchymal stem cells/marrow stromal cells (MSC) represent a promising tool for stem cell-based clinical trials in amyotrophic lateral sclerosis (ALS). We present the results of long-term monitoring of 19 ALS patients enrolled in two phase I clinical trials of autologous MSC transplantation. METHODS Nineteen patients (11 male and eightfemale) with ALS were enrolled in two consecutive phase I clinical trials. The patients were followed-up for 6-9 months and then treated with autologous MSC isolated from bone marrow and implanted into the dorsal spinal cord with a surgical procedure. The patients were monitored regularly before and after transplantation with clinical, psychological and neuroradiologic assessments every 3 months, at the tertiary referral ALS center in Novara (Italy), until death. RESULTS Follow-up brain magnetic resonance imaging (MRI) revealed no structural changes (including tumor formation) relative to the baseline throughout the follow-up. There was no deterioration in the psychosocial status and all patients coped well. No clear clinical benefits were detected in these patients but the recruitment and selection of appropriate patients into larger trials will be needed to test the efficacy of the treatment. CONCLUSIONS This study is the first to show the safety of MSC transplantation in the central nervous system during a follow-up of nearly 9 years, and is in support of applying MSC-based cellular clinical trials to neurodegenerative disorders.

Whole-body diffusion-weighted magnetic resonance imaging in the staging of oncological patients: comparison with positron emission tomography computed tomography (PET-CT) in a pilot study

PurposeThe aim of this pilot study was to compare positron emission tomography computed tomography (PET-CT) and whole-body DWIBS in staging oncological patients to determine the staging accuracy of whole-body DWIBS.Materials and methodsWe initiated a prospective, blinded investigation on 29 patients affected by oncological diseases (n=14) or lymphoma (n=15), who underwent fluorodeoxyglucose (FDG)-based PET-CT and whole-body DWIBS for restaging purposes. Magnetic resonance (MR) imaging was conducted with a multistack (n=4) DWIBS pulse sequence. Images were read independently by two experienced radiologists and one nuclear physician. Statistical analysis assessed interobserver agreement and diagnostic accuracy.ResultsWhole-body DWIBS had a room occupation time of 20 min. Mean postprocessing time was 15 min (range 10–17 min). Mean reading time was 20 min for reader 1 (range 15–25 min) and 18 min for reader 2 (range 13–22 min). Interobserver agreement was almost perfect (=0.93). Reader 1 had a sensitivity of 89.07%, a specificity of 98.5%, and an accuracy of 97.65%, with a positive predictive value (PPV) of 85.48% and a negative predictive value (NPV) of 98.91%. Reader 2 had a sensitivity of 87.39%, a specificity of 98.39% and a diagnostic accuracy of 97.8%, with a PPV of 88.13% and a NPV of 98.75%.ConclusionsThe whole-body DWIBS protocol provided a fast whole-body examination with high specificity and NPV. One major bias of the study was the inclusion of patients with diffuse disease and advanced disease stage and the heterogeneity of the neoplastic diseases included.RiassuntoObiettivoLo scopo dello studio è il confronto tra la risonanza magnetica con difflusione total-body (WBDWIBS) e la TAC-PET nella stadiazione dei pazienti oncologici al fine di valutarne l’accuratezza diagnostica.Materiali e metodiAbbiamo avviato uno studio prospettico, in cieco, su 29 pazienti oncologici (15 con linfoma e 14 con altre neoplasie), che si sono sottoposte nel loro normale percorso diagnostico a TAC-PET con fluro-desossi-glucosio (FDG) e anche ad un’indagine con WB-DWIBS, per restaging di malattia. L’esame RM è stato condotto con una sequenza DWIBS acquisita in multipli pacchetti (4). Le immagini sono state lette indipendentemente da due radiologi esperti e un medico nucleare non consapevoli del quadro clinico dei pazienti. Sono stati calcolati la concordanza inter-osservatore e l’accuratezza diagnostica.RisultatiIl protocollo WB-DWIBS ha occupato la macchina per un totale di 20 minuti. Il tempo medio di post-elaborazione è stato di 15 minuti (10–17). Il tempo di lettura medio è stato di 20 minuti per il lettore 1 (15–25) e 18 minuti per il lettore 2 (13–22). L’agreement tra i due radiologi è risultata quasi perfetta (κ=0,93). Rispettivamente i due radiologi hanno avuto una sensibilità del 89,07% e 87,39%, specificità del 98,5% e del 98,39%, accuratezza diagnostica del 97,65% e 97,8% per i due lettori, PPV del 85,48% e 88,13% e NPV 98,91 e 98,75%.ConclusioniIl protocollo WB-DWIBS è risultato un esame total-body veloce, con elevata specificità e NPV. Un difetto dello studio è sicuramente l’arruolamento di pazienti con lesioni multiple disseminate, l’eterogeneità della casistica.

Role of diffusion-weighted imaging in the differential diagnosis of benign and malignant lesions of the chest-mediastinum.

PurposeWe retrospectively evaluated the role of diffusion-weighted imaging (DWI) with fat and background signal suppression in the differential diagnosis of benign and malignant lesions of the chest-mediastinum by calculating the mean apparent diffusion coefficient (ADC) values.Materials and methodsThirty-four patients with lung nodules/mediastinal masses underwent magnetic resonance (MR) imaging of the chest with conventional and DWI sequences. All patients had been previously studied with computed tomography (CT). After magnetic resonance (MR) imaging the patients underwent transthoracic CT-guided biopsy or mediastinoscopy. After the histopathological diagnosis had been obtained, the lesions were retrospectively divided into five groups: adenocarcinomas (n=16), squamous cell carcinomas (n=12), chronic pneumonias (n=2), malignant mediastinal tumours (n=2) and typical carcinoids (n=2). We compared ADC values in the different lesion groups using the Mann-Whitney U test.ResultsThere were statistically significant differences (p<0.05) between ADC values of benign and malignant lesions. Using an ADC value of 1.25×10−3 mm2/s as a threshold, we were able to differentiate malignant from benign lesions with 91% diagnostic accuracy, 90% sensitivity, 100% specificity, 100% positive predictive value and 57% negative predictive value.ConclusionsShort-tau inversion-recovery echo-planar imaging (STIR-EPI) sequences applied to the chest-mediastinum provided potentially useful images for the differential diagnosis of benign and malignant lesions.RiassuntoObiettivoL’obiettivo del nostro lavoro è stato valutare retrospettivamente il ruolo delle sequenze pesate in diffusione con soppressione del segnale del grasso e del background nella diagnostica differenziale di lesioni benigne e maligne del distretto toraco-mediastinico, attraverso il calcolo dei valori medi del coefficiente di diffusione apparente (ADC).Materiali e metodiTrentaquattro pazienti portatori di noduli polmonari/masse mediastiniche, già sottoposti a tomografia computerizzata (TC) del torace sono stati sottoposti a risonanza magnetica (RM) del torace con sequenze pesate in diffusione. Dopo l’esame RM i pazienti sono stati sottoposti a biopsia transtoracica TC-guidata o a mediastinoscopia. Retrospettivamente, dopo aver ottenuto la diagnosi istopatologica, le lesioni sono state suddivise in cinque gruppi: adenocarcinomi (n=16), carcinomi squamocellulari (n=12), polmoniti croniche (n=2), tumori maligni mediastinici (n=2), carcinoidi tipici (n=2). Abbiamo confrontato i valori medi di ADC calcolati nei diversi gruppi utilizzando il test U di Mann-Whitney.RisultatiAbbiamo ottenuto differenze statisticamente significative (p<0,05) tra i valori di ADC delle lesioni benigne e maligne. Utilizzando come valore soglia un valore di ADC di 1,25×10−3 mm2/s è stato possibile differenziare lesioni maligne dalle benigne con un’accuratezza diagnostica del 91%, sensibilità del 90%, specificità del 100%, valore predittivo positivo del 100% e valore predittivo negativo del 57%.ConclusioniLe sequenze short tau inversion recoveryecho-planar imaging (STIR-EPI) applicate al distretto toraco-mediastinico forniscono immagini potenzialmente utili per la diagnosi differenziale di lesioni benigne e maligne.

Cerebral neoplastic enhancing lesions: Multicenter, randomized, crossover intraindividual comparison between gadobutrol (1.0 M) and gadoterate meglumine (0.5 M) at 0.1 mmol Gd/kg body weight in a clinical setting

OBJECTIVE Two macrocyclic extracellular contrast agents, one-molar neutral gadobutrol and ionic gadoterate meglumine, were compared to determine the overall preference for one or the other in a clinical setting. MATERIALS AND METHODS Multicenter, randomized, single-blind, intra-individually controlled, comparison study with a corresponding blinded read. Efficacy analysis was based on 136 patients who underwent identical MRI examinations: group A first received 1.0M gadobutrol followed by 0.5M gadoterate meglumine 48 h to 7 days later; group B had a reversed administration order. Three independent blinded readers assessed off-site their overall diagnostic preference (primary efficacy parameter) based on a matched pairs approach. RESULTS Superiority of gadobutrol over gadoterate meglumine was demonstrated for the qualitative assessment of overall preference across all readers by a statistically significant difference between both contrast agents for this primary endpoint. Preferences in lesion enhancement (secondary endpoint) were also found significantly in favor of gadobutrol. For preference in lesion delineation from surrounding tissue/edema and for internal structure only a trend towards a higher proportion for gadobutrol was found (except for internal structure reported by one reader, which showed a result of statistical significance). Lesion contrast and relative lesion enhancement (quantitative parameters) were statistically significantly higher for gadobutrol compared to gadoterate meglumine. CONCLUSION Contrast-enhanced MRI of neoplastic brain lesions at a dose of 0.1 mmol Gd/kg body weight, assessed in a standardized off-site blinded reading, results in a significantly higher qualitative and quantitative preference for gadobutrol compared to gadoterate meglumine.

Corpus callosum abnormalities in Tourette syndrome: an MRI-DTI study of monozygotic twins

Background Tourette syndrome (TS) is a chronic neurodevelopmental disorder characterised by the presence of multiple motor and phonic tics. Recent brain imaging investigations with diffusion tensor imaging (DTI) techniques found reduced measures of connectivity in the corpus callosum of children with TS compared with healthy controls, thus raising the hypothesis that the reduced interhemispherical connectivity in TS reflects neural plasticity processes. Methods We assessed corpus callosum white-matter connectivity with fractional anisotropy (FA) index from magnetic resonance-DTI in two monozygotic twins (male sex; age 20) discordant for the diagnosis of TS. Results Both conventional morphological magnetic resonance images and fibre-tracking reconstruction failed to show any difference between the two twins. On the other hand, mean corpus callosum FA values were significantly lower in the affected twin than in the unaffected twin (p<0.01). The differences in FA values were highest in the posterior portions of the corpus callosum, and lowest in the central area. Conclusions Our findings of reduced interhemispherical white-matter connectivity in the affected twin support the hypothesis that plastic remodelling in the corpus callosum possibly represents an adaptation mechanism in TS.

Reducing operator radiation exposure during cardiac resynchronization therapy

AIMS To quantify the reduction in equivalent dose at operators hand that can be achieved by placement of a radiation-absorbing drape (RADPAD) during long-lasting cardiac resynchronization therapy (CRT) procedures. METHODS AND RESULTS This is a prospective observational study that included 22 consecutive patients with drug-refractory heart failure who underwent implantation of a CRT device. The cases were randomly assigned to Group A (11 cases), performed without RADPAD, and to Group B (11 cases), performed using RADPAD. Dose equivalent at the examiners hand was measured as H(p)(0.07) and as a time-adjusted H(p)(0.07) rate (mGy/min) with a direct reading dosimeter. The mean fluoroscopy time was 20.8 ± 7.7 min and the mean dose area product (DAP) was 118.6 ± 45.3 Gy cm(2). No significant differences were found between body mass index, fluoroscopy time, and DAP between patients examined with or without RADPAD. The correlation between the fluoroscopy time and the DAP was high (R(2) = 0.94, P < 0.001). Mean dose and dose rate measurement without the RADPAD at the finger and hand were H(p)(0.07) = 1.27 ± 0.47 mGy per procedure and H(p)(0.07) rate = 0.057 ± 0.011 mGy/min, respectively. The dosage was reduced with the RADPAD to H(p)(0.07) = 0.48 ± 0.20 (P < 0.05) and to H(p)(0.07) rate = 0.026 ± 0.008 (P < 0.001), respectively. CONCLUSION A mean reduction of 54% in the equivalent dose rate to the operators hand can be achieved with the use of RADPAD. The use of the RADPAD in CRT devices implantation will make unlikely the necessity of limiting the yearly number of implants for high volume operators.

Estimated Radiation Exposure from Medical Imaging in Hemodialysis Patients

Radiation exposure accompanying medical imaging associates with cancer risk. Patients with recurrent or chronic diseases may be especially at risk, because they may undergo more of these procedures. The aim of this study was to assess the individual cumulative effective doses (CEDs), which quantify radiation from medical imaging procedures, in a cohort of 106 hemodialysis patients during a median follow-up of 3 years. We retrospectively calculated individual radiation exposures by collecting the number and type of radiologic procedures from hospital records. We also estimated organ doses for computed tomography procedures. The mean and median annual CEDs were 21.9 and 11.7 mSv per patient-year, respectively. The mean and median total CEDs per patient during the study period were 57.7 and 27.3 mSv, respectively. By radiation dose group, we classified 22 patients as low (<3 mSv/yr), 51 as moderate (3 to <20 mSv/yr), 22 as high (20 to <50 mSv/yr), and 11 as very high (≥50 mSv/yr). Seventeen patients had a total CED >100 mSv, a value associated with a substantial increase in risk for cancer-related mortality. Of the total CED,s 76% was a result of CT scanning. The annual CED significantly associated with age and transplant waitlist status. In summary, this study shows that a significant fraction of surviving hemodialysis patients during a 3-year period receives estimated radiation doses that may put them at an increased risk for cancer.

Can MRI Predict Which Patients Are Most Likely to Benefit from Percutaneous Positioning of Volume-Adjustable Balloon Devices?

Purpose: To assess whether magnetic resonance imaging (MRI) is useful in predicting which patients affected by stress urinary incontinence (SUI) will benefit from a new anti-incontinence therapy named adjustable continence therapy (ACT™). Methods: We prospectively evaluated a group of 25 female patients affected by SUI and treated with ACT. Before and after treatment all patients were clinically assessed by physical examination, urodynamic evaluation and pad test. All patients had an MR examination before and 3 and 12 months after ACT surgery to compare the position of the bladder neck in relation to the pubococcygeal line (PCL). Results: 21/25 (84%) patients were improved; 16 (64%) of these patients were dry and 5 (20%) significantly improved. Before treatment, the mean PCL distance was significantly different (p < 0.01) between the responsive and the non-responsive groups. Conclusions: MRI provides an effective radiological method to predict the efficacy of the ACT.

Delineation of target volume for radiotherapy of high-grade gliomas by 99m Tc-MIBI SPECT and MRI fusion.

Background and Purpose:Computed tomography (CT) and magnetic resonance imaging (MRI) are traditionally used for treatment planning of high-grade glioma. 99mTc-methoxy-isobutyl-isonitrile (MIBI) single-photon emission computed tomography (SPECT) showed high sensitivity and specificity in literature series. In the present study, it was investigated how the information provided by 99mTc-MIBI SPECT and MRI fusion could affect target delineation for radiotherapy of high-grade glioma.Patients and Methods:21 patients with high-grade glioma were studied by MRI and 99mTc-MIBI SPECT imaging. The gross tumor volume (GTV) was outlined on MRI (MRI-GTV) and SPECT images (SPECT-GTV). Three additional volumes were analyzed: the (MRI+SPECT)-GTV representing the whole amount of MRI-GTV plus SPECT-GTV, the (MRI&SPECT)-GTV identified by the overlapping region of MRI-GTV and SPECT-GTV, and the (SPECT/MRI)-GTV identified by the extension of SPECT-GTV outside MRI-GTV.Results:MRI contrast-enhanced and 99mTc-MIBI SPECT-positive lesions were found in all 21 patients. The average SPECT-GTV was slightly larger than the average MRI-GTV, with greater difference for resected than for unresected cases. The average increment of (MRI+SPECT)-GTV compared to MRI-GTV was 33%, being significantly higher for resected than for unresected cases (p = 0.006).Conclusion:The fusion of 99mTc-MIBI SPECT and MRI significantly affected the delineation of the target volume identified by MRI alone.Hintergrund und Ziel:Computertomographie (CT) und Magnetresonanztomographie (MRT) werden üblicherweise für die Bestrahlungsplanung maligner Gliome verwendet. Die Single-Photon-Emissionscomputertomographie (SPECT) mit 99mTc-Methoxy-Isobutyl-Isonitril (MIBI) zeigte in Literaturserien eine hohe Sensitivität und Spezifität. In der vorliegenden Studie wurde untersucht, wie die durch 99mTc-MIBI-SPECT- und MRT-Bildfusion bereitgestellten Informationen die Zielvolumendefinition maligner Gliome beeinflussen können.Patienten und Methodik:21 Patienten mit malignen Gliomen wurden mit MRT und 99mTc-MIBI-SPECT untersucht. Das makroskopische Tumorvolumen („gross tumor volume“ [GTV]) wurde auf MRT-(MRT-GTV) und SPECT-Bildern (SPECT-GTV) umrissen. Drei zusätzliche Volumen wurden analysiert: (MRT+SPECT)-GTV, d.h. die Summe von MRT-GTV und SPECT-GTV, (MRT&SPECT)-GTV, d.h. der sich überlappende Bereich von MRT-GTV und SPECT-GTV, und (SPECT/MRT)-GTV, d.h. die Ausbreitung des SPECT-GTV außerhalb des MRT-GTV.Ergebnisse:MRT-kontrastverstärkte und 99mTc-MIBI-SPECT-positive Läsionen wurden bei allen 21 Patienten gefunden. Das durchschnittliche SPECT-GTV war etwas größer als das durchschnittliche MRT-GTV, wobei sich ein größerer Unterschied für operierte als für nicht operierte Patienten fand. Die durchschnittliche Zunahme des (MRT+SPECT)-GTV betrug im Vergleich zum MRT-GTV 33% und war bei operierten Patienten signifikant größer als bei nicht operierten Patienten (p = 0,006).Schlussfolgerung:Die Bildfusion von 99mTc-MIBI-SPECT und MRT hatte erheblichen Einfluss auf die durch alleinige MRT bestimmte Zielvolumendefinition, insbesondere bei operierten Patienten.

Cumulative radiation dose from medical imaging in chronic adult patients.

Chronic patients require ongoing care that results in repeated imaging and exposure to ionizing radiation for both diagnostic and therapeutic purposes. This is of concern due to the long-term effects of radiation exposure, namely the association between radiation and increased cancer risk. In this study, the scientific literature on cumulated dose of radiation accrued from medical imaging by 4 cohorts of chronic patients (cardiac disease, end-stage kidney disease, inflammatory bowel disease, and patients undergoing endovascular aortic repair) was systematically reviewed. We found that the cumulative effective dose is moderate in cardiac and inflammatory bowel disease patients, high in end-stage kidney disease patients, and very high in endovascular aortic repair patients. We concluded that radiation burden of medical imaging is high in selected cohorts of chronic patients. Efforts should be implemented to reduce this cumulative dose and its potential attendant risks.