Prediction of osteoporotic fragility re-fracture with lumbar spine DXA-based derived bone strain index: a multicenter validation study.

A new qualitative index of bone strength, based on finite element analysis and named bone strain index, has been recently developed from lumbar DXA scan. This study shows that BSI predicts subsequent re-fracture in osteoporotic patients affected by fragility fractures. INTRODUCTION: Dual-energy X-ray absorptiometry (DXA) can provide quantitative (bone mineral density, BMD) and qualitative (trabecular bone score, TBS) indexes of bone status, able to predict fragility fractures in most osteoporotic patients. A new qualitative index of bone strength, based on finite element analysis and named bone strain index (BSI), has been recently developed from lumbar DXA scan. This study presents the validation results of BSI prediction for re-fracture in osteoporotic patients with fragility fractures. METHODS: In three academic hospitals, 234 consecutive fractured patients with primary osteoporosis (209 females) performed a spine X-ray for the calculation of spine deformity index (SDI) and DXA densitometry for BMD, TBS and BSI at the basal time and in the follow-up at each clinical check. A subsequent fracture was considered as one unity increase of SDI. RESULTS: For each unit increase of the investigated indexes, the univariate hazard ratio of re-fracture, 95% CI, p value and proportionality test p value are for age 1.040, 1.017-1.064, 0.0007 and 0.2529, respectively, and for BSI 1.372, 1.038-1.813, 0.0261 and 0.5179, respectively. BSI remained in the final multivariate model as a statistically significant independent predictor of a subsequent re-fracture (1.332, 1.013-1.752 and 0.0399) together with age (1.039, 1.016-1.064 and 0.0009); for this multivariate model proportionality test, p value is 0.4604. CONCLUSIONS: BSI appears to be a valid DXA index of prediction of re-fracture, and it can be used for a more refined risk assessment of osteoporotic patients.

Technique and protocols for cardiothoracic time-resolved contrast-enhanced magnetic resonance angiography sequences: a systematic review.

AIM: To review contrast medium administration protocols used for cardiothoracic applications of time-resolved, contrast-enhanced magnetic resonance angiography (MRA) sequences. MATERIALS AND METHODS: A systematic search of the literature (Medline/EMBASE) was performed to identify articles utilising time-resolved MRA sequences, focusing on type of sequence, adopted technical parameters, contrast agent (CA) issues, and acquisition workflow. Study design, year of publication, population, magnetic field strength, type, dose, and injection parameters of CA, as well as technical parameters of time-resolved MRA sequences were extracted. RESULTS: Of 117 retrieved articles, 16 matched the inclusion criteria. The study design was prospective in 9/16 (56%) articles, and study population ranged from 5 to 185 patients, for a total of 506 patients who underwent cardiothoracic time-resolved MRA. Magnetic field strength was 1.5 T in 13/16 (81%), and 3 T in 3/16 (19%) articles. The administered CA was gadobutrol (Gadovist) in 6/16 (37%) articles, gadopentetate dimeglumine (Magnevist) in 5/16 (31%), gadobenate dimeglumine (MultiHance) in 2/16 (13%), gadodiamide (Omniscan) in 2/16 (13%), gadofosveset trisodium (Ablavar, previously Vasovist) in 1/16 (6%). CA showed highly variable doses among studies: fixed amount or based on patient body weight (0.02-0.2 mmol/kg) and was injected with a flow rate ranging 1-5 ml/s. Sequences were TWIST in 13/16 (81%), TRICKS in 2/16 (13%), and CENTRA 1/16 articles (6%). CONCLUSION: Time-resolved MRA sequences were adopted in different clinical settings with a large spectrum of technical approaches, mostly in association with different CA dose, type, and injection method. Further studies in relation to specific clinical indications are warranted to provide a common standardised acquisition protocol.

Epicardial adipose tissue volume in patients with coronary artery disease or non-ischaemic dilated cardiomyopathy: evaluation with cardiac magnetic resonance imaging.

AIM: To compare the amount of epicardial adipose tissue (EAT) in patients with coronary artery disease (CAD) or non-ischaemic dilated cardiomyopathy (NIDCM) with that in patients with negative cardiac magnetic resonance imaging (CMR). MATERIALS AND METHODS: One hundred and fifty patients (median age 57 years, interquartile range [IQR] 46-66 years) who underwent CMR were evaluated retrospectively: 50 with CAD, 50 with NIDCM, and 50 with negative CMR. For each patient, the EAT mass index (EATMI) to body surface area, end-diastolic volume index (EDVI), end-systolic volume index (ESVI), stroke volume (SV), ejection fraction (EF) for both ventricles, and left ventricle (LV) mass index were estimated. Intra and inter-reader reproducibility was tested in a random subset of 30 patients, 10 for each group. Mann-Whitney U test, Kruskal-Wallis test, Spearman's correlation, and Bland-Altman statistics were used. RESULTS: The EATMI in CAD patients (median 15.7 g/m2, IQR 8.3-25.7) or in NIDCM patients (15.9 g/m2, 11.5-18.1) was significantly higher than that in negative CMR patients (9.1 g/m2, 6-12; p<0.001 both). No significant difference was found between CAD and NIDCM patients (p=1.000). A correlation between EATMI and LV mass index was found in NIDCM patients (r=0.455, p=0.002). Intra- and inter-reader reproducibility were up to 80% and 72%, respectively. CONCLUSION: Patients with NIDCM or CAD exhibited an increased EATMI in comparison to negative CMR patients. CMR can be used to estimate EAT with good reproducibility.

Meta-analysis of agreement between MRI and pathologic breast tumour size after neoadjuvant chemotherapy.

BACKGROUND: Magnetic resonance imaging (MRI) has been proposed to guide breast cancer surgery by measuring residual tumour after neoadjuvant chemotherapy. This study-level meta-analysis examines MRI's agreement with pathology, compares MRI with alternative tests and investigates consistency between different measures of agreement. METHODS: A systematic literature search was undertaken. Mean differences (MDs) in tumour size between MRI or comparator tests and pathology were pooled by assuming a fixed effect. Limits of agreement (LOA) were estimated from a pooled variance by assuming equal variance of the differences across studies. RESULTS: Data were extracted from 19 studies (958 patients). The pooled MD between MRI and pathology from six studies was 0.1 cm (95% LOA: -4.2 to 4.4 cm). Similar overestimation for MRI (MD: 0.1 cm) and ultrasound (US) (MD: 0.1 cm) was observed, with comparable LOA (two studies). Overestimation was lower for MRI (MD: 0.1 cm) than mammography (MD: 0.4 cm; two studies). Overestimation by MRI (MD: 0.1 cm) was smaller than underestimation by clinical examination (MD: -0.3 cm). The LOA for mammography and clinical examination were wider than that for MRI. Percentage agreement between MRI and pathology was greater than that of comparator tests (six studies). The range of Pearson's/Spearman's correlations was wide (0.21-0.92; 16 studies). Inconsistencies between MDs, percentage agreement and correlations were common. CONCLUSION: Magnetic resonance imaging appears to slightly overestimate pathologic size, but measurement errors may be large enough to be clinically significant. Comparable performance by US was observed, but agreement with pathology was poorer for mammography and clinical examination. Percentage agreement can provide supplementary information to MDs and LOA, but Pearson's/Spearman's correlation does not provide evidence of agreement and should be avoided. Further comparisons of MRI and other tests using the recommended methods are warranted.

Bone mineral density differences between femurs of scoliotic patients undergoing dual-energy X-ray absorptiometry.

AIM: To investigate whether a difference exists in the bone mineral density (BMD) between femurs in scoliotic patients undergoing dual-energy X-ray absorptiometry (DXA) and whether this difference is related to spine convexity. MATERIALS AND METHODS: Of 1080 consecutive patients who underwent DXA, 127 had lumbar scoliosis seen at DXA. Further, after excluding 30 patients with previous osteoporotic fractures, metallic/image artefacts, soft-tissue calcifications, the BMD differences between femurs of 97 scoliotic patients (94 females; mean age 67 ± 11 years) were analysed. Femurs were classified as ipsilateral or contralateral to the spine convexity. Least significant change was used as a threshold of measurement precision. Differences between femoral neck BMD in respect of and regardless of spine convexity were calculated for each patient. Student's t-test and Wilcoxon's signed-rank test were used to assess significance. RESULTS: Fifty-nine of 97 patients (61%) had left-sided scoliosis. Osteoporosis was found in 32/97 patients (33%), osteopenia in 54/97 (56%), and 11/97 (11%) had a normal T-score. Of 97 patients, 46 (47%) had ipsilateral BMD < contralateral BMD. Regardless of spine convexity, 66/97 patients (68%) had different BMD values between femurs. Among them, variation of densitometric diagnosis was seen in 29/66 patients (44%), and in 29/97 patients overall (30%). CONCLUSION: Differences in the femoral neck BMD exist between femurs of scoliotic patients undergoing DXA. Thus, bilateral femoral DXA acquisition is recommended.

Prevalence of cerebral aneurysms in patients treated for left cardiac myxoma: a prospective study.

AIM: To estimate the prevalence of cerebral aneurysms in patients previously treated for left cardiac myxoma (LCM). MATERIALS AND METHODS: This prospective institutional review board-approved study included patients treated for LCM. All patients treated at our institution (IRCCS Policlinico San Donato, Italy) were telephoned and those enrolled underwent unenhanced brain magnetic resonance imaging (MRI) using sagittal T1-weighted turbo spin-echo (TSE); axial T2-weighted TSE; axial fluid-attenuated inversion-recovery; axial echo-planar diffusion-weighted; and three-dimensional time-of-flight angiographic sequences. RESULTS: Seventy-six patients were telephoned, and data regarding their clinical history since tumor resection were obtained for 49 patients (64%). Four of the 49 (8%) patients were deceased, one due to a cerebral hemorrhage from a ruptured cerebral aneurysm 8 years after tumor resection. One patient had a pacemaker preventing MRI. Of the remaining 44 patients, 31 refused MRI and 13 were enrolled (10 females; mean age 64 years). Three of the 13 (23%; two females; 59-78 years) were diagnosed with a cerebral aneurysm, from 2 mm to 4-5 mm in diameter, involving the right middle cerebral artery (n = 2) or the right internal carotid artery (n = 1). Including the deceased patient, the resulting prevalence was 4/14 (29%). CONCLUSION: From this preliminary study, one-third of patients treated for LCM may present with a cerebral aneurysm. Longitudinal large studies are needed to further clarify this matter.

Contrast-enhanced MR imaging of the breast: association between asymmetric increased breast vascularity and ipsilateral cancer in a consecutive series of 197 patients.

PURPOSE: This study was done to estimate the diagnostic performance of an asymmetric increase in breast vascularity (AIBV) for ipsilateral cancer. MATERIALS AND METHODS: A total of 197 patients without previous breast interventions underwent bilateral contrast-enhanced (gadoterate meglumine, 0.1 mmol/kg) magnetic resonance (MR) imaging. Vessels >-2 mm in diameter and ≥ 3 cm in length were counted on maximum intensity projections: a difference ≥ 2 in number between the two breasts was considered AIBV. Pathology or ≥ 1 year follow-up served as a reference standard. The difference in sensitivity of AIBV between invasive and ductal carcinoma in situ (DCIS) as well as the association between AIBV and the diameter of invasive lesions or the histological grade were evaluated using χ(2) test. RESULTS: Pathology revealed 82 malignancies and 20 benign lesions: 70 invasive carcinomas (57 ductal, nine lobular, three mucinous, one papillary) and 12 DCIS: 10 fibroadenomas, two papillomas, two atypical ductal hyperplasias and six other benign lesions. The remaining 95 patients were negative at follow-up. Sensitivity of AIBV was 74% (61/82), specificity 94% (108/115), accuracy 86% (169/197), positive predictive value 90% (61/68) and negative predictive value 84% (108/129). Sensitivity for invasive cancers (80%; 56/70) was significantly higher than that for DCIS (42%; 5/12) (p<0.001). For invasive cancers, sensitivity was 40% (2/5) for lesions ≤ 9 mm in diameter, 69% (9/13) for those 10-14 mm, 79% (15/19) for those 15-19 mm and 91% (30/33) for those ≥ 20 mm (p<0.001). The G3 lesion rate was 49% (27/55) among true positives and only 7% (1/14) among false negatives (p=0.009). CONCLUSIONS: An association between AIBV and ipsilateral cancer exists, particularly for invasive cancers ≥ 20 mm or with high pathologic grade.

[Clinical indications for the use of cardiac MRI. By the SIRM Study Group on Cardiac Imaging]. / Indicazioni cliniche per l'utilizzo della cardio RM. A cura del Gruppo di lavoro della Sezione di Cardio-Radiologia della SIRM.

Cardiac magnetic resonance (CMR) is considered an useful method in the evaluation of many cardiac disorders. Based on our experience and available literature, we wrote a document as a guiding tool in the clinical use of CMR. Synthetically we describe different cardiac disorders and express for each one a classification, I to IV, depending on the significance of diagnostic information expected.

Computer-aided diagnosis for dynamic contrast-enhanced breast MRI of mass-like lesions using a multiparametric model combining a selection of morphological, kinetic, and spatiotemporal features.

PURPOSE: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a radiological tool for the detection and discrimination of breast lesions. The aim of this study is to evaluate a computer-aided diagnosis (CAD) system for discriminating malignant from benign breast lesions at DCE-MRI by the combined use of morphological, kinetic, and spatiotemporal lesion features. METHODS: Fifty-four malignant and 19 benign breast lesions in 51 patients were retrospectively evaluated. Images were acquired at two centers at 1.5 T. Mass-like lesions were automatically segmented after image normalization and elastic coregistration of contrast-enhanced frames. For each lesion, a set of 28 3D features were extracted: ten morphological (related to shape, margins, and internal enhancement distribution); nine kinetic (computed from signal-to-time curves); and nine spatiotemporal (related to the variation of the signal between adjacent frames). A support vector machine (SVM) was trained with feature subsets selected by a genetic search. Best subsets were composed of the most frequent features selected by majority rule. The performance was measured by receiver operator characteristics analysis with a stratified tenfold cross-validation and bootstrap method for confidence intervals. RESULTS: SVM training by the three separated classes of features resulted in an area under the curve (AUC) of 0.90 ± 0.04 (mean ± standard deviation), 0.87 ± 0.06, and 0.86 ± 0.06 for morphological, kinetic, and spatiotemporal feature, respectively. Combined training with all 28 features resulted in AUC of 0.96 ± 0.02 obtained with a selected feature subset composed by two morphological, one kinetic, and two spatiotemporal features. CONCLUSIONS: Quantitative combination of morphological, kinetic, and spatiotemporal features is feasible and provides a higher discriminating power than using the three different classes of features separately.

Magnetic resonance imaging of painful total hip replacement: detection and characterisation of periprosthetic fluid collection and interobserver reproducibility.

PURPOSE: The purpose of our study was to demonstrate the diagnostic value of magnetic resonance imaging (MRI) when measuring and characterising periprosthetic fluid collections in patients with painful hip prosthesis and to provide an estimation of interobserver reproducibility. MATERIALS AND METHODS: Nineteen patients (mean age 59±13 years) with painful total hip replacement and clinical suspicion of infection underwent MRI. Images were reviewed blindly by two musculoskeletal radiologists with different levels of experience who evaluated the presence/absence of soft tissue oedema or fluid collection (when present, three-plane maximal diameters were measured; involvement of skin/subcutaneous/deep tissues or prosthesis were estimated; fluid was classified as serous/purulent/haematic according to signal behaviour). Interobserver agreement was calculated (Cohen's ). RESULTS: A total of 26 MRI studies were carried out (three patients underwent two and two patients underwent three MRI examinations). Both readers detected soft tissue oedema (13/26, 50%) or fluid collection (21/26, 81%) and characterised the fluid as serous (9/21, 43%), purulent (8/21, 38%) or haematic (4/21, 19%). The collection involved skin/subcutaneous tissues (16/21, 76%), deep soft tissues (19/21, 91%) or the implant (12/21, 57%). For all evaluations, interobserver agreement was complete (=1). No significant differences were found between the measurements of the collections (p>0.258). CONCLUSIONS: MRI is highly reproducible in detection, localisation, quantification, and characterisation of fluid collections when the presence of implant infection is clinically suspected.

Clinical indications for cardiac computed tomography. From the Working Group of the Cardiac Radiology Section of the Italian Society of Medical Radiology (SIRM).

Cardiac computed tomography (CCT) has grown as a useful means in different clinical contexts. Technological development has progressively extended the indications for CCT while reducing the required radiation dose. Even today there is little documentation from the main international scientific societies describing the proper use and clinical indications of CCT; in particular, there are no complete guidelines. This document reflects the position of the Working Group of the Cardiac Radiology Section of the Italian Society of Radiology concerning the indications for CCT.

Cardiac magnetic resonance: impact on diagnosis and management of patients with congenital cardiovascular disease.

AIM: To estimate the clinical impact of cardiac magnetic resonance (CMR) in patients with congenital cardiovascular disease (CCD). MATERIALS AND METHODS: Since 2003, 1.5T CMR was used at our university hospital to evaluate morphology, cardiac kinetics, aortic and pulmonary flow, and vascular anatomy in patients with CCD. The present study considered a consecutive series of these patients from 2003 to 2006. A paediatric cardiologist judged our reports as expected or unexpected and, secondarily, as not reliable (level 0), describing findings already known (level 1), not changing therapy/suggested lifestyle (level 2), changing therapy/suggested lifestyle (level 3) or changing diagnosis (level 4). RESULTS: CMR reports were judged to be expected in 187/214 (87%) and unexpected in 27/214 (13%). Less than 2% of CMRs were judged as levels 0 or 1, 66% as level 2, and 5% as level 4. During 2005-2006 the clinical impact improved toward higher impact levels (p<0.001, chi-square test). CONCLUSIONS: In patients with CCD, more than one in 10 CMR reports were unexpected to cardiologists and over seven in 10 prompted a change of diagnosis or therapy.

Renal volume assessment with 3D ultrasound.

PURPOSE: This study was undertaken to determine the accuracy of 3D ultrasound (US) in assessing renal volume, with multislice computed tomography (MSCT) considered as the gold standard. MATERIALS AND METHODS: Forty-nine patients (30 men, 19 women; age range 30-82 years) underwent abdominal contrast-enhanced MSCT and 3D-US performed with a 3.5-MHz 3D/4D convex-array probe. The results of the two modalities were compared with the Wilcoxon test. Variability between the two measurements was determined with the Bland-Altman method and reported in terms of bias and coefficient of repeatability (CoR). RESULTS: Mean values obtained were 210 ml with MSCT and 192 ml with 3D-US (p<0.001). Analysis of variability per patient between MSCT and 3D-US showed a bias of 19 ml, a CoR of 47 ml and an accuracy of 78%, with an average 3D-US underestimation of 19 ml (9%). Analysis of variability per kidney showed a bias of 9 ml, a CoR of 34 ml and an accuracy of 80%. CONCLUSIONS: Three-dimensional US is a valuable technique for monitoring renal volume, whereas MSCT may be reserved for assessing renal anatomy and relationships with neighbouring organs.

Myocardial delayed enhancement using a single dose (0.1 mmol/kg) of gadobenate dimeglumine: contrast resolution versus intraventricular blood and viable myocardium.

PURPOSE: This study was done to estimate delayed enhancement (DE) contrast resolution of infarcted myocardium (IM) relative to intraventricular blood (IB) and viable myocardium (VM) using gadobenate dimeglumine (Gd-BOPTA). MATERIALS AND METHODS: After approval from the Ethics Committee, we retrospectively evaluated 21 consecutive patients (61+/-10 years) with a healed myocardial infarction who underwent 1.5-T magnetic resonance (MR) imaging using an inversion-recovery-prepared turbo gradient-echo sequence 10 minutes after injection of 0.1 mmol/kg of Gd-BOPTA. Signal intensity (SI) was measured in arbitrary units (au) for IM, IB, VM, and outside the patient. Contrast-to-noise ratio (CNR) was calculated for IM to IB and IM to VM. Seven consecutive patients (59+/-6 years) with a healed myocardial infarction studied with similar technique but with 0.1 mmol/kg of gadoterate meglumine (Gd-DOTA) served as the control group. The Mann-Whitney U test was used to compare groups. RESULTS: Mean SI of IM was 44+/-16 au for Gd-BOPTA and 20+/-6 au for Gd-DOTA (p<0.001), that of IB 35+/-15 au and 14+/-5 au (p=0.016), and that of VM 7+/-3 au and 5+/-2 au (p=0.116), respectively. Mean IM to IB CNR was 10+/-7 for Gd-BOPTA and 8+/-5 for Gd-DOTA (p=0.836), that of IM to VM was 45+/-27 and 18+/-6, respectively (p=0.012). CONCLUSIONS: Gd-BOPTA at 0.1 mmol/kg produced a higher myocardial DE and an IM to VM CNR than a single dose of Gd-DOTA. No significant difference was observed for IM to IB CNR.

[MRI and CT in the evaluation of congenital heart diseases]. / RM e TC nella valutazione delle cardiopatie congenite.

Magnetic resonance imaging (MRI) allows a static and cinetic study of congenital heart diseases avoiding patient exposure to ionizing radiation. It allows for evaluating cardiac morphology, heart function with accurate ventricular volume estimation, flow quantification with gradient and regurgitant fraction estimation, and vascular anatomy (aortic, pulmonary and proximal coronary vessels). Computed tomography (CT), with greater spatial resolution, allows for evaluating proximal and distal coronary arteries, vascular and pericardial calcifications, metal structures such as stents and prosthetic valves. The use of MRI or CT in young and adult patients with congenital heart diseases should be assessed case by case through a close collaboration between cardiologists and radiologists, aiming at an optimal tradeoff between expected diagnostic gain and biological cost in terms of ionizing radiation exposure and contrast material administration.

High prevalence of simple kidney cysts in patients with primary hyperparathyroidism.

PTH has been demonstrated to promote renal epithelial cell proliferation and cysts development. The study aimed to evaluate the prevalence of kidney cysts in patients with primary hyperparathyroidism (PHPT). The prevalence of renal cysts diagnosed at abdominal ultrasound examinations in 172 PHPT patients (59.4+/-15.1 yr, mean age+/-SD; female/male 2.8) with preserved renal function was compared with that observed in 210 age- and sex-matched healthy controls. All patients underwent clinical, serum, and urine evaluations, and bone mineralization assessment by dual X-ray absorptiometry. Simple kidney cysts occurred with a higher prevalence in both male and female PHPT patients in comparison with healthy controls (34.9% vs 16.2% p<0.001). Kidney cysts were absent in patients younger than 39 yr, whereas they were present in one third of PHPT patients in their 4th, 5th, and 6th decades, increasing up to 45% after the age of 70. Multiple renal cysts were larger and more frequent than single cysts. PHPT patients with renal cysts were affected by a more active PTH secretion than patients without renal cysts as indicated by significant higher hypercalcemia and lower tubular maximal phosphate (TmP) reabsorption, while renal function, the occurrence of kidney stones, and osteoporosis were similar in both groups. Reduced TmP values were associated with about 3-fold increase in the risk of kidney cysts. In conclusion, simple renal cysts might be considered as a benign kidney complication of PHPT and might be related to the action of the chronic elevated PTH levels on tubular epithelial cells.

Primary hyperparathyroidism: can ultrasonography be the only preoperative diagnostic procedure?

PURPOSE: The purpose of our study was to assess the role of ultrasonography (US) before surgical treatment of primary hyperparathyroidism. MATERIALS AND METHODS: We retrospectively evaluated 77 patients (60 women, 17 men; mean age 59 years) with primary hyperparathyroidism who underwent parathyroid US prior to surgery. Sixty-five of 77 (84%) patients had undergone (99m)Tc- sestamibi (MIBI) scintigraphy. The results were correlated with the surgical and histopathological findings. RESULTS: Surgery revealed 85 abnormal parathyroid glands in 77 patients (70 adenomas, 15 hyperplasias). The locations of the parathyroid glands were typical cervical (n=77), thyrothymic ligament (n=3), carotid sheath (n=2), and mediastinum (n=3). In two patients, intrathyroid microadenoma was diagnosed by histopathology. Seventy-four enlarged glands in 64 patients were correctly identified at US. Per-patient sensitivity and positive predictive values, respectively, were 84% (64/76) and 99% (64/65) for US, 68% (44/65) and 100% (44/44) for scintigraphy and 91% (59/65) and 98% (59/60) for both techniques combined. We weighed 63 out of 85 glands, obtaining a value of 1,004+/-1,564 mg; 460 mg (mean+/-standard deviation; median). CONCLUSIONS: Preoperative detection and localisation of enlarged parathyroid glands can be based on US, an inexpensive and widely available method, limiting the use of scintigraphy to those cases with negative and/or doubtful findings on US.

A novel neurocognitive approach for placebo analgesia in neurocognitive disorders.

Neural correlates of placebo analgesia (PA) in patients with neurocognitive disorders have not yet been elucidated. The present study aimed to evaluate how and to what extent executive (dys)functions of the medial prefrontal cortex (MPFC) may be related to PA. To this end, twenty-three subjects complaining of different cognitive deficits (from mild cognitive impairment likely due to Alzheimer's disease to mild AD) were recruited. PA was investigated by a well-known experimental venipuncture pain paradigm (open versus hidden [O-H] application of lidocaine). Patients also underwent a comprehensive neuropsychological evaluation and a functional magnetic resonance imaging (fMRI) GO/No-GO task for eliciting selective activation of the MPFC. Selected neuropsychological variables were correlated to the OH-PA paradigm. The association between the fMRI response on the "No-GO" versus "GO" contrast and PA was investigated over the whole-brain by regression analysis. We showed the existence of a relationship between a lower PA and MPFC dysfunctions through the neuropsychological and fMRI assessment. A separate voxel-based morphometry (VBM) analysis controlled for possible influence of grey matter (GM) volume reduction on both fMRI results and PA. fMRI results were not directly affected by, and therefore independent of, disease-specific GM atrophy, which was indeed located more anteriorly within the rostral anterior cingulate and inversely correlated with PA. Our findings shed new light on the underestimated contribution of executive (dys)functions mediated by the MPFC (response-inhibition, self-monitoring and set-shifting abilities) in PA pathogenesis, with a special purely (i.e. independently from brain structural alterations) functional role played by the MCC. Results are discussed in terms of possible clinical relevance in the management of patients with neurocognitive disorders.