Alessandro Stecco

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.

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.

Chronic Cerebrospinal Venous Insufficiency Is Not Associated with Multiple Sclerosis and Its Severity: A Blind-Verified Study

Background Chronic Cerebrospinal Venous Insufficiency (CCSVI) has been associated with multiple sclerosis (MS) with a risk ranging from as high as two-hundred-fold to a protective effect. However, not all studies were blinded, and the efficacy of blinding was never assessed. Objective To evaluate the association of CCSVI with MS in a cross-sectional blinded study and look for any association of CCSVI with the severity of MS. Methodology/Principal Findings The Echo-color Doppler examination was carried out in accordance with Zamboni’s five criteria in 68 consecutive MS patients and 68 healthy controls, matched by gender and age (±5 years). Four experienced neurosonologists, blinded to the status of cases and controls, performed the study and were then asked to guess the status (case or control) of each participant. The number of positive CCSVI criteria was similar in the two groups. CCSVI, defined as the presence of two or more criteria, was detected in 21 cases (30.9%) and 23 controls (33.8%), with an OR of 0.9 (95%CL = 0.4–1.8, p = 0.71). The prevalence of CCSVI was related to age in cases (OR increasing from 0.2 to 1.4), but not in controls. CCSVI positive (N = 21) and negative (N = 47) MS patients were similar in clinical type, age at disease onset, disability, and fatigue. Disease duration was longer (16.5±9.8 years) in CCSVI positive than negative patients (11.5±7.4; p = 0.04). The operators correctly guessed 34/68 cases (50%) and 45/68 controls (66%) (p = 0.06), indicating a different success of blinding. Conclusions/Significance CCSVI was not associated with MS itself, nor its severity. We cannot rule out the possibility that CCSVI is a consequence of MS or of aging. Blinding of sonographers is a key point in studying CCSVI and its verification should be a requisite of future studies.

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.

MRI can assess glenoid bone loss after shoulder luxation: inter- and intra-individual comparison with CT

ObjectiveComputed tomography (CT) is the gold standard for evaluating glenoid bone loss in patients with glenohumeral dislocations. The aim of this study was to verify if magnetic resonance imaging (MRI) can quantify the area of bone loss without any significant difference from CT.Materials and methodsTwenty-three patients, who had experienced one or more post-traumatic unilateral glenohumeral dislocations, underwent MRI and CT. MR and multiplanar reconstruction CT images were acquired in the sagittal plane: the glenoid area and the area of bone loss were calculated using the PICO method. Mean values, percentages, Cohen’s kappa coefficients and Bland-Altman plots were all used to confirm the working hypothesis.ResultsThe mean glenoid surface area was 575.29 mm2 as measured by MRI, and 573.76 mm2 as measured by CT; the calculated mean glenoid bone loss was respectively 4.38% and 4.34%. The interobserver agreement was good (k>0.81), and the coefficient of variance was 5% of the mean value using both methods. The two series of measurements were within two standard deviations of each other.ConclusionsMRI is a valid alternative to CT for measuring glenoid bone loss in patients with glenohumeral dislocation.RiassuntoObiettivoLa tomografia computerizzata (TC) è il gold standard nella valutazione del danno osseo glenoideo in pazienti con lussazione gleno-omerale. Lo scopo dello studio è verificare se la risonanza magnetica (RM) può quantificare l’area di danno osseo senza significative differenze rispetto alla TC.Materiali e metodiVentitre pazienti con uno o più episodi di lussazione traumatica gleno-omerale unilaterale sono stati sottoposti a RM e TC. Sono state acquisite le ricostruzioni MPR in TC e le immagini RM sul piano sagittale: la misura dell’area della glena e la misura del danno osseo sono state effettuate utilizzando il metodo PICO. Medie, percentuali, test di concordanza K di Cohen e Bland-Altman test sono stati elaborati per confermare l’ipotesi di lavoro.RisultatiLa misura dell’area glenoidea risulta di 575,29 mm2 con RM e di 573,76 mm2 con TC e le rispettive misure del deficit glenoideo sono di 4,38% e 4,34%. La concordanza inter-osservatore in TC e RM è risultata buona con k>0,81, il coefficiente di varianza è <5% del valor medio sia in TC che RM. Le due serie di misurazioni sono comprese entro 2 deviazioni standard.ConclusioniLa RM è una valida alternativa alla TC nella misurazione del danno osseo glenoideo in pazienti con dislocazioni gleno-omerali.

Power estimation for non-standardized multisite studies

A concern for researchers planning multisite studies is that scanner and T1-weighted sequence-related biases on regional volumes could overshadow true effects, especially for studies with a heterogeneous set of scanners and sequences. Current approaches attempt to harmonize data by standardizing hardware, pulse sequences, and protocols, or by calibrating across sites using phantom-based corrections to ensure the same raw image intensities. We propose to avoid harmonization and phantom-based correction entirely. We hypothesized that the bias of estimated regional volumes is scaled between sites due to the contrast and gradient distortion differences between scanners and sequences. Given this assumption, we provide a new statistical framework and derive a power equation to define inclusion criteria for a set of sites based on the variability of their scaling factors. We estimated the scaling factors of 20 scanners with heterogeneous hardware and sequence parameters by scanning a single set of 12 subjects at sites across the United States and Europe. Regional volumes and their scaling factors were estimated for each site using Freesurfers segmentation algorithm and ordinary least squares, respectively. The scaling factors were validated by comparing the theoretical and simulated power curves, performing a leave-one-out calibration of regional volumes, and evaluating the absolute agreement of all regional volumes between sites before and after calibration. Using our derived power equation, we were able to define the conditions under which harmonization is not necessary to achieve 80% power. This approach can inform choice of processing pipelines and outcome metrics for multisite studies based on scaling factor variability across sites, enabling collaboration between clinical and research institutions.

Shoulder MR arthrography: in vitro determination of optimal gadolinium dilution as a function of field strength.

To find the optimal contrast agent dilution to maximize signal intensity (SI), signal‐to‐noise ratio (SNR), and contrast‐to‐noise ratio (CNR) in shoulder MR arthrography using MR systems operating at different magnetic field strengths.

Endovascular treatment of intracranial aneurysms with flow-diverter stents: preliminary single-centre experience

PurposeThis paper reports our preliminary experience with the endovascular treatment of intracranial aneurysms using flow-diverter stents (FDs) and compares it with the literature data.Materials and methodsFrom May 2009 to April 2012, 28 patients (6 men and 22 women; mean age, 54 years) with a total of 35 aneurysms were treated with FDs. We evaluated postprocedural technical success and long-term efficacy, with follow-up examinations performed at 3–7 days [computed tomography (CT)/magnetic resonance (MR) angiography] and at 3, 6 and 12 months (digital subtraction angiography, DSA). A total of 43 FDs were placed, 36 Pipeline and 7 Silk.ResultsA total of 30 procedures were performed (two patients were treated twice). Technical success was 96.6%, with one case of postprocedural death; the aneurysm exclusion rate at 3, 6 and 12 months was 60%, 73% and 89%, respectively. There was no case of acute stent thrombosis, and only two cases of nonsignificant stenosis. All covered side branches were patent, except one case of steno-occlusion of the ophthalmic artery.ConclusionsOur results are consistent with the literature and demonstrate the effectiveness and safety of FDs in selected cases of cerebral aneurysm (wide neck, fusiform, blister-like).RiassuntoObiettivoScopo del presente lavoro è riportare la nostra esperienza nel trattamento endovascolare degli aneurismi cerebrali mediante stent a diversione di flusso (FD), confrontandola con i dati della letteratura.Materiali e metodiDa maggio 2009 ad aprile 2012 sono stati trattati mediante FD 28 pazienti (6 maschi e 22 femmine; età media 54 anni) portatori di 35 aneurismi cerebrali. Abbiamo valutato il successo tecnico procedurale e l’efficacia a distanza mediante angiotomografia computerizzata (TC) o angio-risonanza magnetica (RM) a 3–7 giorni, quindi angiografia digitale a sottrazione (DSA) a 3, 6 e 12 mesi. Sono stati posizionati complessivamente 43 FD, 36 Pipeline e 7 Silk.RisultatiComplessivamente sono stati eseguiti 30 interventi (due ritrattamenti a 3 mesi per copertura parziale del colletto aneurismatico). Abbiamo ottenuto il successo tecnico nel 96,6% dei casi, con un caso (3,4%) di insuccesso esitato in decesso post-operatorio. L’esclusione dal circolo dell’aneurisma è stata a 3, 6 e 12 mesi rispettivamente del 60%, 73% ed 89%. Non abbiamo osservato nessun caso di trombosi intra-stent, solo due casi di stenosi lieve intra-stent, risoltesi poi al followup; in tutti i casi i vasi collaterali ricoperti dagli stent sono risultati pervi, eccetto un caso di steno-occlusione dell’arteria oftalmica.ConclusioniI risultati da noi ottenuti, in linea con i dati della letteratura, documentano che il trattamento degli aneurismi cerebrali mediante FD rappresenta un’opzione sicura ed efficace in casi selezionati (aneurismi a largo colletto, fusiformi, blister-like), con buoni risultati nel tempo.