Early Prenatal Ultrasound and Molecular Diagnosis of Apert Syndrome: Case Report with Postmortem CT-Scan and Chondral Plate Histology.

Background Apert syndrome is characterized by craniosynostosis, midface hypoplasia and symmetric syndactyly. Case report: A 36-year-old mother, G2P1 underwent an ultrasound scan at 19 week's gestation. There was craniosynostosis, brachi-turricephaly and bilateral hand syndactyly. Genomic DNA from amniocentesis revealed the mutation C758C>Gp. (Pro to Arg substitution) at 252 of the exon 8 of the FGFR2 encoding for Apert syndrome. The pregnancy was terminated. Femoral chondral plate histology showed an increased interstitial matrix between bony trabeculae. Compared with normal, the trabeculae were thinner, more irregular with numerous osteoclasts suggesting abnormal bone remodeling. Hands and feet had an abrupt transition between resting and proliferating cartilage. Conclusion: Apert syndrome has increased intertrabecular matrix, thin trabeculae, increased remodeling, and irregular transition between the maturing and mineralization zones in the femur, and abnormal abrupt transition between the resting and proliferating cartilage in the fingers and toes.

Comparative X-ray morphometry of prenatal osteogenesis imperfecta type 2 and thanatophoric dysplasia: a contribution to prenatal differential diagnosis.

OBJECTIVE: The purpose of the paper was to assess the morphometric parameters to improve the specificity of the ultrasound (US) signs for the early differential diagnosis between two lethal dysplasias, as thanatophoric dysplasia (TD) and osteogenesis imperfecta type 2 (OI-2). METHOD: The diaphyseal length and the bowed shape of long bones associated with vertebral body dimension assessment were investigated in a group of 14 pregnancy terminations carried out in the time period 2007-2013. The definitive diagnosis was established after pregnancy termination by means of skeletal standardized X-rays, histopathology and gene analysis. RESULTS: TD and OI-2 long bones were significantly shorter than controls. No significant differences were observed between the two dysplasias. The bowing angle was higher in OI-2; a true angulation or eventually axial displacement was present only in the latter. Furthermore, they did not show any evidence of vertebral collapse. The thanatophoric dysplasia presented less bowed long bones, and never true angulation. The spine was steadily characterized by flattened anterior vertebral bodies. CONCLUSION: Long bone shortening is not a sufficient and accurate sign for early sonographic differential diagnosis between TD and OI-2. Angled diaphysis, axial diaphyseal displacement and a conserved vertebral body height in the prenatal period support the diagnosis of osteogenesis imperfecta type 2, while moderately regular bowed diaphysis associated with platyspondyly that of thanatophoric dysplasia.

Next-generation sequencing and its initial applications for molecular diagnosis of systemic auto-inflammatory diseases.

OBJECTIVES: Systemic auto-inflammatory disorders (SAIDs) are a heterogeneous group of monogenic diseases sharing a primary dysfunction of the innate immune system. More than 50% of patients with SAID does not show any mutation at gene(s) tested because of lack of precise clinical classification criteria and/or incomplete gene screening. To improve the molecular diagnosis and genotype interpretation of SAIDs, we undertook the development of a next-generation sequencing (NGS)-based protocol designed to simultaneous screening of 10 genes. METHODS: Fifty patients with SAID, already genotyped for the respective causative gene(s), were massively sequenced for the coding portions of MEFV, MVK, TNFRSF1A, NLRP3, NLRP12, NOD2, PSTPIP1, IL1RN, LPIN2 and PSMB8. Three different bioinformatic pipelines (Ion Reporter, CLC Bio Genomics Workbench, GATK-based in-house workflow) were compared. RESULTS: Once resulting variants were compared with the expected mutation list, no workflow turned out to be able to detect all the 79 variants known in the 50 DNAs. Additional variants were also detected, validated by Sanger sequencing and compared to assess true and false positive detection rates of the three workflows. Finally, the overall clinical picture of 34 patients was re-evaluated in the light of the new mutations found. CONCLUSIONS: The present gene panel has resulted suitable for molecular diagnosis of SAIDs. Moreover, genotype-phenotype correlation has confirmed that the interpretation of NGS data in patients with an undefined inflammatory phenotype is remarkably difficult, thus supporting the need of evidence-based and validated clinical criteria to be used concurrently with the genetic analysis for the final diagnosis and classification of patients with SAIDs.

Association of achondroplasia with sagittal synostosis and scaphocephaly in two patients, an underestimated condition?

We report on two patients with an unusual combination of achondroplasia and surgically treated sagittal synostosis and scaphocephaly. The most common achondroplasia mutation, p.Gly380Arg in fibroblast growth factor receptor 3 (FGFR3), was detected in both patients. Molecular genetic testing of FGFR1, FGFR2, FGFR3 and TWIST1 genes failed to detect any additional mutations. There are several reports of achondroplasia with associated craniosynostosis, but no other cases of scaphocephaly in children with achondroplasia have been described. Recently it has been demonstrated that FGFR3 mutations affect not only endochondral ossification but also membranous ossification, providing new explanations for the craniofacial hallmarks in achondroplasia. Our report suggests that the association of isolated scaphocephaly and other craniosynostoses with achondroplasia may be under recognized.

Thanatophoric dysplasia. Correlation among bone X-ray morphometry, histopathology, and gene analysis.

OBJECTIVE: Documentation through X-ray morphometry and histology of the steady phenotype expressed by FGFR3 gene mutation and interpolation of mechanical factors on spine and long bones dysmorphism. MATERIALS AND METHODS: Long bones and spine of eight thanatophoric dysplasia and three age-matched controls without skeletal dysplasia were studied after pregnancy termination between the 18th and the 22nd week with X-ray morphometry, histology, and molecular analysis. Statistical analysis with comparison between TD cases and controls and intraobserver/interobserver variation were applied to X-ray morphometric data. RESULTS: Generalized shortening of long bones was observed in TD. A variable distribution of axial deformities was correlated with chondrocyte proliferation inhibition, defective seriate cell columns organization, and final formation of the primary metaphyseal trabeculae. The periosteal longitudinal growth was not equally inhibited, so that decoupling with the cartilage growth pattern produced the typical lateral spurs around the metaphyseal growth plates. In spine, platyspondyly was due to a reduced height of the vertebral body anterior ossification center, while its enlargement in the transversal plane was not restricted. The peculiar radiographic and histopathological features of TD bones support the hypothesis of interpolation of mechanical factors with FGFR3 gene mutations. CONCLUSIONS: The correlated observations of X-ray morphometry, histopathology, and gene analysis prompted the following diagnostic workup for TD: (1) prenatal sonography suspicion of skeletal dysplasia; (2) post-mortem X-ray morphometry for provisional diagnosis; (3) confirmation by genetic tests (hot-spot exons 7, 10, 15, and 19 analysis with 80-90% sensibility); (4) in negative cases if histopathology confirms TD diagnosis, research of rare mutations through sequential analysis of FGFR3 gene.

Clinical impact of MEFV mutations in children with periodic fever in a prevalent western European Caucasian population.

OBJECTIVE: To evaluate the actual impact of MEFV mutations on clinical manifestations associated with fever attacks in Caucasian children with periodic fever. METHODS: 113 children carrying MEFV mutations (44 with mutations in two alleles, 69 heterozygous) and 205 children negative for mutations in genes associated with periodic fevers were analysed. The following groups of patients were considered: patients carrying two high penetrance mutations (M694V, M694I, M680I); one high, one low penetrance mutation; two low penetrance mutations; one high penetrance mutation; one low penetrance mutation; genetically negative patients. RESULTS: Patients with two MEFV mutations displayed a shorter duration of fever attacks and higher prevalence of a positive family history than patients carrying one MEFV mutation and genetically negative patients. Severe abdominal pain, chest pain and pleurisy were also more frequent in patients with two MEFV mutations compared with children with one MEFV mutation and genetically negative patients. Conversely, a higher frequency of exudative and erythematous pharyngitis, enlargement of cervical lymph nodes, aphthous stomatitis and non-specific skin rash was observed in genetically negative patients and, to a lesser extent, in patients with one MEFV mutation. The frequency of 'familial Mediterranean fever (FMF)-like symptoms' decreases from patients carrying two high penetrance mutations towards patients with a single low penetrance mutation with an opposite trend for 'periodic fever, aphthous stomatitis, pharyngitis, adenitis-like symptoms'. CONCLUSIONS: This clinical observation supports recent findings contrasting the notion of FMF being a pure autosomal recessive disorder associated with recurrence of mutations leading to loss of protein function. A dosage effect could be invoked, giving rise to symptom onset even in the presence of one wild-type allele.

Late gadolinium enhancement by cardiovascular magnetic resonance is complementary to left ventricle ejection fraction in predicting prognosis of patients with stable coronary artery disease.

BACKGROUND: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) predicts adverse prognosis in patients with stable coronary artery disease (CAD). However, the interaction with conventional risk factors remains uncertain. Our aim was to assess whether the extent of LGE is an independent predictor of adverse cardiac outcome beyond conventional risk factors, including left ventricle ejection fraction (LVEF). METHODS: We enrolled 376 patients (88% males, 64 ± 11 years) with stable CAD, who underwent LGE assessment and a detailed conventional evaluation (clinical and pharmacological history, risk factors, ECG, Echocardiography). During a follow-up of 38 ± 21 months, 56 events occurred (32 deaths, 24 hospitalizations for heart failure). RESULTS: LGE and LVEF showed the strongest univariate associations with end-points (HR: 13.61 [95%C.I.: 7.32-25.31] for LGE ≥ 45% of LV mass; and 12.34 [6.80-22.38] for LVEF ≤ 30%; p < 0.0001). Multivariate analysis identified baseline LVEF, loop diuretic therapy, moderate-severe mitral regurgitation and pulmonary hypertension as significant predictors among conventional risk factors. According to a step-wise approach, LGE showed strong association with prognosis as well (5.25 [2.64-10.43]; p < 0.0001). LGE significantly improved the model predictability (chi-square 239 vs 221, F-test p < 0.0001) with an additive effect on the prognostic power of LVEF, which however retained its prognostic power (4.89 [2.50-09.56]; p < 0.0001). Patients with LGE ≥ 45% and/or LVEF ≤ 30% had much worse prognosis compared to patients without risk factors (annual event rates of 43% vs 3%; p < 0.0001). Interestingly LGE was a significant predictor when all cause mortality was analyzed as the only endpoint. CONCLUSIONS: This study demonstrates that LGE assessed by CMR is a robust independent non-invasive marker of prognosis in stable CAD patients. LGE can integrate the available metrics to substantially improve risk stratification.

Apert syndrome with fused thalami.

Apert syndrome (Acrocephalosyndactyly type I; AS) is a rare but well-known autosomal dominant disorder characterized by craniosynostosis, midface hypoplasia, bony/cutaneous syndactyly of fingers and toes as well as a variety of associated congenital anomalies involving the brain, heart, limbs and other organ systems. We report the case of a fetus with molecularly confirmed Apert syndrome and additional fusion of the thalamic nuclei. Various central nervous system anomalies, have been reported in patients with AS. However, as far as we know cases of fused thalami in Apert syndrome have never been reported so far.

Craniosynostosis: prenatal diagnosis by means of ultrasound and SSSE-MRI. Family series with report of neurodevelopmental outcome and review of the literature.

INTRODUCTION: Craniosynostosis is a condition characterized by a premature closure of one or more skull sutures and refers to a wide spectrum of cranial malformation with an estimated birth of 1:2,000-1:4,000 live births. Four receptors (FGFR 1, FGFR 2, FGFR 3, FGFR 4) involving mutation in the fibroblast growth factor have been identified. MATERIALS AND METHODS: Two cases occurred in the same family and diagnosed prenatally by means of ultrasound, and antenatal and postnatal MR imaging are reported. Molecular biology regarding identification of craniosynostosis type has been analyzed. A revision of the medical literature is also provided. CONCLUSION: The premature closure of sagittal suture is characterized by a disproportionately large occipito-frontal and short biparietal diameter (scaphocephaly). The prenatal ultrasound diagnosis of craniosynostosis in utero may be difficult and be suspected when the cephalic index, the cranial shape or the fetal face shape are abnormal. Fetal karyotype is recommended and DNA testing plays a critical role in achieving an appropriate diagnosis, when possible. The prognosis of craniosynostosis is primarily dependent on the presence of associated anomalies as craniosynostosis are correlated with three to fivefold increased risk for cognitive disabilities.

Magnetic resonance investigations in Brugada syndrome reveal unexpectedly high rate of structural abnormalities.

AIMS: Recent data suggest that sub-clinical structural abnormalities may be part of the Brugada syndrome (BrS) phenotype, a disease traditionally thought to occur in the structurally normal heart. In this study, we carried out detailed assessment of cardiac morphology and function using cardiac magnetic resonance imaging (CMRI). METHODS AND RESULTS: Thirty consecutive patients with BrS were compared with 30 sex- (26/4 male/female), body surface area- (+/-0.2 m(2)), and age-matched (+/-5 years) normal volunteers. CMRI exam included long- and short-axis ECG-gated breath-hold morphological T1-TSE sequences for fatty infiltration and cine-SSFP sequences for kinetic assessment. Fatty infiltration was not found in any subject. Patients with BrS compared with normal subjects showed higher incidence of mild right ventricle (RV) wall-motion abnormalities [15 (50%) vs. 5 (17%) subjects (P = 0.006) with reduced radial fractional shortening in more than two segments], reduction of outflow tract ejection fraction (49 +/- 11% vs. 55 +/- 10%; P = 0.032), enlargement of the inflow tract diameter (46 +/- 4 vs. 41 +/- 5 mm, P < 0.001 in short-axis; 46 +/- 4 vs. 42 +/- 5 mm, P = 0.001 in four-chamber long-axis view) and area (22 +/- 2 vs. 20 +/- 3 cm(2); P = 0.050), and of global RV end-systolic volume (34 +/- 10 vs. 30 +/- 6 mL/m(2); P = 0.031) but comparable outflow tract dimensions, global RV end-diastolic volume, left ventricle parameters, and atria areas. CONCLUSION: CMRI detects a high prevalence of mild structural changes of the RV, and suggests further pathophysiological complexity in BrS. Prospective studies to assess the long-term evolution of such abnormalities are warranted.

Thanatophoric dysplasia type I associated with increased nuchal translucency in the first trimester: Early prenatal diagnosis using combined ultrasonography and molecular biology.

A case of thanatophoric dysplasia (TD) type I associated with severely increased nuchal translucency at first trimester screening for Down syndrome is reported. A 38-year-old woman, G2P1, with previous uneventful pregnancy, was referred for amniocentesis at 16 weeks due to positive first trimester integrated test. Amniocentesis revealed a 46,XX fetus. At 16 weeks gestation, the ultrasound examination of the fetus revealed a narrow chest, short ribs, and a generalized severe shortening of the long bones. The patient underwent a follow-up scan at 19 weeks which demonstrated ultrasound findings consistent with severe rhizomelic micromelia. A wide prenatal panel of gene mutations related with skeletal dysplasia was performed. Nucleotidic sequence using QF-PCR on exons 7,10, 15, 19 of the fibroblast growth factor receptor 3 (FGFR3) demonstrated a 742 C>T (R248C) mutation, which resulted in an Arg248Cys substitution in heterozygous state, leading to a prenatal diagnosis of thanatophoric dysplasia type I. The early diagnosis of this lethal form of skeletal dysplasia directed the prenatal counseling and allowed appropriate obstetric management. Necropsy, post-mortem x-ray, and histologic analysis of the growth plate might aid the diagnosis of TD type I.

Autistic symptoms in Greig cephalopolysyndactyly syndrome: a family case report.

BACKGROUND: Greig cephalopolysyndactyly syndrome is a rare multiple congenital anomaly syndrome characterized by the triad of polysyndactyly (preaxial or mixed preaxial and postaxial), macrocephaly, and ocular hypertelorism. Little is known about the neuropsychological phenotype and the developmental features of this syndrome. CASE PRESENTATION: We describe the clinical features of a 7-year-old Italian white boy affected by Greig cephalopolysyndactyly syndrome in comorbidity with autism spectrum disorder and the case of his 45-year-old white father, carrying the same point deletion (c.3677del) in the GLI3 gene and showing subclinical autistic symptoms. We performed a neuropsychiatric assessment of cognitive, adaptive, socio-communicative, and behavioral skills of the child. Concurrently, the father underwent his first psychiatric evaluation of cognitive skills and autistic symptoms. CONCLUSIONS: We report the first clinical description of an association between autistic symptoms and Greig cephalopolysyndactyly syndrome in two members of the same family with the same genetic point deletion. Further research is required in order to draw an accurate conclusion regarding the association between Greig cephalopolysyndactyly syndrome and autism.

Germline mosaicism in achondroplasia detected in sperm DNA of the father of three affected sibs.

We describe a sib recurrence for achondroplasia with parents of average stature. The three sibs shared the paternal allele and all carried the same causal mutation in the fibroblast growth factor receptor 3 gene (FGFR3): G > A nt1138 (Gly380Arg). We were able to identify this mutation on sperm DNA confirming paternal germinal mosaicism. Our family shows that a more precise definition of the recurrence risk is feasible using this approach, based on a single DNA test, which could be offered in selected cases.

To treat or not to treat: comparison of different criteria used to determine whether weight loss is to be recommended.

BACKGROUND: Excess body fat is a major risk factor for disease primarily due to its endocrine activity. In recent years several criteria have been introduced to evaluate this factor. Nevertheless, treatment need is currently assessed only on the basis of an individual's Body Mass Index (BMI), calculated as body weight (in kg) divided by height in m2. The aim of our study was to determine whether application of the BMI, compared to adiposity-based criteria, results in underestimation of the number of subjects needing lifestyle intervention. METHODS: We compared treatment need based on BMI classification with four adiposity-based criteria: percentage body fat (%BF), considered both alone and in relation to metabolic syndrome risk (MS), waist circumference (WC), as an index of abdominal fat, and Body Fat Mass Index (BFMI, calculated as fat mass in kg divided by height in m2) in 63 volunteers (23 men and 40 women, aged 20 - 65 years). RESULTS: According to the classification based on BMI, 6.3% of subjects were underweight, 52.4% were normal weight, 30.2% were overweight, and 11.1% were obese. Agreement between the BMI categories and the other classification criteria categories varied; the most notable discrepancy emerged in the underweight and overweight categories. BMI compared to almost all of the other adiposity-based criteria, identified a lower percentage of subjects for whom treatment would be recommended. In particular, the proportion of subjects for whom clinicians would strongly recommend weight loss on the basis of their BMI (11.1%) was significantly lower than those identified according to WC (25.4%, p = 0.004), %BF (28.6%, p = 0.003), and MS (33.9%, p = 0.002). CONCLUSION: The use of the BMI alone, as opposed to an assessment based on body composition, to identify individuals needing lifestyle intervention may lead to unfortunate misclassifications. Population-specific data on the relationships between body composition, morbidity, and mortality are needed to improve the diagnosis and treatment of at-risk individuals.

A Method for Manufacturing Oncological Phantoms for the Quantification of 18F-FDG PET and DW-MRI Studies.

The aim of this work was to develop a method to manufacture oncological phantoms for quantitation purposes in 18F-FDG PET and DW-MRI studies. Radioactive and diffusion materials were prepared using a mixture of agarose and sucrose radioactive gels. T2 relaxation and diffusion properties of gels at different sucrose concentrations were evaluated. Realistic oncological lesions were created using 3D-printed plastic molds filled with the gel mixture. Once solidified, gels were extracted from molds and immersed in a low-radioactivity gel simulating normal background tissue. A breast cancer phantom was manufactured using the proposed method as an exploratory feasibility study, including several realistic oncological configurations in terms of both radioactivity and diffusion. The phantom was acquired in PET with 18F-FDG, immediately after solidification, and in DW-MRI the following day. Functional volumes characterizing the simulated BC lesions were segmented from PET and DW-MRI images. Measured radioactive uptake and ADC values were compared with gold standards. Phantom preparation was straightforward, and the time schedule was compatible with both PET and MRI measurements. Lesions appeared on 18F-FDG PET and DW-MRI images as expected, without visible artifacts. Lesion functional parameters revealed the phantom's potential for validating quantification methods, in particular for new generation hybrid PET-MRI systems.

Nerve Fascicles and Epineurium Volume Segmentation of Peripheral Nerve Using Magnetic Resonance Micro-neurography.

RATIONALE AND OBJECTIVES: The aims of this study were to propose a semiautomated technique to segment and measure the volume of different nerve components of the tibial nerve, such as the nerve fascicles and the epineurium, based on magnetic resonance microneurography and a segmentation tool derived from brain imaging; and to assess the reliability of this method by measuring interobserver and intraobserver agreement. MATERIALS AND METHODS: The tibial nerve of 20 healthy volunteers (age range = 23-69; mean = 47; standard deviation = 15) was investigated at the ankle level. High-resolution images were obtained through tailored microneurographic sequences, covering 28 mm of nerve length. Two operators manually segmented the nerve using the in-phase image. This region of interest was used to mask the nerve in the water image, and two-class segmentation was performed to measure the fascicular volume, epineurial volume, nerve volume, and fascicular to nerve volume ratio (FNR). Interobserver and intraobserver agreements were calculated. RESULTS: The nerve structure was clearly visualized with distinction of the fascicles and the epineurium. Segmentation provided absolute volumes for nerve volume, fascicular volume, and epineurial volume. The mean FNR resulted in 0.69 with a standard deviation of 0.04 and appeared to be not correlated with age and sex. Interobserver and intraobserver agreements were excellent with alpha values >0.9 for each parameter investigated, with measurements free of systematic errors at the Bland-Altman analysis. CONCLUSIONS: We concluded that the method is reproducible and the parameter FNR is a novel feature that may help in the diagnosis of neuropathies detecting changes in volume of the fascicles or the epineurium.

Effects of active music therapy on the normal brain: fMRI based evidence.

The aim of this study was to investigate the neurophysiological bases of Active Music Therapy (AMT) and its effects on the normal brain. Twelve right-handed, healthy, non-musician volunteers were recruited. The subjects underwent 2 AMT sessions based on the free sonorous-music improvisation using rhythmic and melodic instruments. After these sessions, each subject underwent 2 fMRI scan acquisitions while listening to a Syntonic (SP) and an A-Syntonic (AP) Production from the AMT sessions. A 3 T Discovery MR750 scanner with a 16-channel phased array head coil was used, and the image analysis was performed with Brain Voyager QX 2.8. The listening to SP vs AP excerpts mainly activated: (1) the right middle temporal gyrus and right superior temporal sulcus, (2) the right middle frontal gyrus and in particular the right precentral gyrus, (3) the bilateral precuneus, (4) the left superior temporal sulcus and (5) the left middle temporal gyrus. These results are consistent with the psychological bases of the AMT approach and with the activation of brain areas involved in memory and autobiographical processes, and also in personal or interpersonal significant experiences. Further studies are required to confirm these findings and to explain possible effects of AMT in clinical settings.

Contrast-enhanced magnetic resonance imaging assessment of scar size in patients with chronic myocardial infarction.

BACKGROUND: In the assessment of myocardial infarction (MI) mass, contrast-enhanced magnetic resonance imaging (CE-MRI) is comparable to single-photon emission computed tomography (SPECT). The aim of the present study was to determine whether the MI area, as assessed at CE-MRI and SPECT, is comparable to mass evaluation. We also compared CE-MRI and SPECT estimates of the MI area with functional evaluations made at echocardiography and kinetic MRI (cine-MRI). METHODS: We used a 1.0 Tesla MRI scanner and an inversion-recovery turboFLASH sequence, a tomographic gamma-camera and second-harmonic ultrasound systems. Two blinded operators assessed the extent of scarring, expressed as a percentage of the whole left ventricle (LV), using a 16-segment model. We studied 55 consecutive patients with a clinically stable healed MI (50 Q wave, 5 non-Q wave). RESULTS: The scar mass was 19+/-23% of the LV at CE-MRI and 21+/-25% at SPECT; the scar area was 29+/-23% of the LV at CE-MRI, 41+/-28% at SPECT, 29+/-31% at cine-MRI, and 32+/-29% at echocardiography. The Bland-Altman bias between CE-MRI and SPECT mass estimations was -2% of the LV with a+/-23% limit of agreement (LOA), while the bias between the area assessments was -12% with a+/-42% LOA. Bias between CE-MRI and functional evaluation by cine-MRI and echocardiography was 0% with a+/-39% LOA and -3% with a+/-36% LOA respectively. Comparing SPECT with cine-MRI and echocardiography the bias was 12% with a+/-52% LOA and 9% with a+/-56% LOA respectively. CONCLUSIONS: CE-MRI has proved to be comparable to SPECT in the assessment of the healed MI mass. Conversely, a high systematic error (high bias and LOA) renders CE-MRI and SPECT assessments of the MI area incomparable. Similarly (high bias and/or LOA) CE-MRI and SPECT estimations of the MI area cannot be compared with functional evaluation by echocardiography or cine-MRI.

Non-invasive coronary angiography with multislice computed tomography. Technology, methods, preliminary experience and prospects.

The recent technical developments in multislice computed tomography (MSCT), with ECG retro-gated image reconstruction, have elicited great interest in the possibility of accurate non-invasive imaging of the coronary arteries. The latest generation of MSCT systems with 8-16 rows of detectors permits acquisition of the whole cardiac volume during a single 15-20 s breath-hold with a submillimetric definition of the images and an outstanding signal-to-noise ratio. Thus the race which, between MSCT, electron beam computed tomography and cardiac magnetic resonance imaging, can best provide routine and reliable imaging of the coronary arteries in clinical practice has recommenced. Currently available MSCT systems offer different options for both cardiac image acquisition and reconstruction, including multiplanar and curved multiplanar reconstruction, three-dimensional volume rendering, maximum intensity projection, and virtual angioscopy. In our preliminary experience including 176 patients suffering from known or suspected coronary artery disease, MSCT was feasible in 161 (91.5%) and showed a sensitivity of 80.4% and a specificity of 80.3%, with respect to standard coronary angiography, in detecting critical stenosis in coronary arteries and artery or venous bypass grafts. These results correspond to a positive predictive value of 58.6% and a negative predictive value of 92.2%. The true role that MSCT is likely to play in the future in non-invasive coronary imaging is still to be defined. Nevertheless, the huge amount of data obtainable by MSCT along with the rapid technological advances, shorter acquisition times and reconstruction algorithm developments will make the technique stronger, and possible applications are expected not only for non-invasive coronary angiography, but also for cardiac function and myocardial perfusion evaluation, as an all-in-one examination.

[Non-invasive coronary angiography by multislice computed tomography: a new diagnostic method?]. / Coronarografia non invasiva mediante tomografia computerizzata multistrato: verso una nuova realtà diagnostica?

A significant improvement in the noninvasive evaluation of coronary anatomy has been obtained after the introduction of the new high-speed multislice computed tomography systems. Images are reconstructed using retrospective ECG-gated protocol along with contrast analysis and three-dimensional display algorithms. The 8 detectors and the reduced tube rotation time of last-generation scanners allow the coverage of the entire heart during a single breath-hold following an intravenous bolus of 120 ml of nonionic contrast. Faster computer software offers submillimeter resolution reconstructions and increased post-processing capabilities, such as quantitative angiography, virtual angioscopy, and calcium score evaluation. At least in this phase of technical development the visualization of side branches of coronary vessels seems to advantage multislice computed tomography with respect to nuclear magnetic resonance and electron-beam computed tomography in the challenge for clinical noninvasive evaluation of coronary microcirculation.