Evidence of disrupted rhombic lip development in the pathogenesis of Dandy-Walker malformation.

Dandy-Walker malformation (DWM) and Cerebellar vermis hypoplasia (CVH) are commonly recognized human cerebellar malformations diagnosed following ultrasound and antenatal or postnatal MRI. Specific radiological criteria are used to distinguish them, yet little is known about their differential developmental disease mechanisms. We acquired prenatal cases diagnosed as DWM and CVH and studied cerebellar morphobiometry followed by histological and immunohistochemical analyses. This was supplemented by laser capture microdissection and RNA-sequencing of the cerebellar rhombic lip, a transient progenitor zone, to assess the altered transcriptome of DWM vs control samples. Our radiological findings confirm that the cases studied fall within the accepted biometric range of DWM. Our histopathological analysis points to reduced foliation and inferior vermian hypoplasia as common features in all examined DWM cases. We also find that the rhombic lip, a dorsal stem cell zone that drives the growth and maintenance of the posterior vermis is specifically disrupted in DWM, with reduced proliferation and self-renewal of the progenitor pool, and altered vasculature, all confirmed by transcriptomics analysis. We propose a unified model for the developmental pathogenesis of DWM. We hypothesize that rhombic lip development is disrupted through either aberrant vascularization and/or direct insult which causes reduced proliferation and failed expansion of the rhombic lip progenitor pool leading to disproportionate hypoplasia and dysplasia of the inferior vermis. Timing of insult to the developing rhombic lip (before or after 14 PCW) dictates the extent of hypoplasia and distinguishes DWM from CVH.

Contrast-enhanced ultrasound in the diagnosis of pediatric focal nodular hyperplasia and hepatic adenoma: interobserver reliability.

BACKGROUND: Focal nodular hyperplasia and hepatic adenoma are rare liver tumors in which specific features on contrast-enhanced ultrasound (US) have been reported but are little known in children. OBJECTIVE: To assess the interobserver agreement in diagnosing and differentiating focal nodular hyperplasia and hepatic adenoma in children using established adult contrast-enhanced US characteristics. MATERIALS AND METHODS: Thirty children with a definite or probable diagnosis of focal nodular hyperplasia or hepatic adenoma on magnetic resonance imaging (MRI)/histology who underwent contrast-enhanced US studies were included. Typical and additional contrast-enhanced US features of focal nodular hyperplasia and hepatic adenoma were included. The lesions were classified as definite/probable focal nodular hyperplasia, definite/probably hepatic adenoma or unclassified. The interobserver kappa of contrast-enhanced US characteristics was calculated. RESULTS: Focal nodular hyperplasia and hepatic adenoma in children demonstrate contrast-enhanced US characteristics similar to those in adults. Among the nine lesions with confirmed histological diagnosis, correct diagnosis was made in 7 (77.8%) based on contrast-enhanced US criteria. Two lesions were unclassified by both observers due to a mixed arterial filling pattern. Interobserver kappa for contrast-enhanced US diagnosis was 0.64 (P<0.0001). CONCLUSION: There is a good interobserver kappa for separating focal nodular hyperplasia from hepatic adenoma in children using established adult contrast-enhanced US features.

Highlights on MRI of the fetal body.

Fetal MRI is a level III diagnostic tool performed subsequently a level II prenatal ultrasound (US), in cases of inconclusive ultrasonographic diagnosis or when a further investigation is required to confirm or improve the diagnosis, to plan an appropriate pregnancy management. Fetal MRI plays an increasingly important role in the prenatal diagnosis of fetal neck, chest and abdominal malformations, even if its role has been amply demonstrated, especially, in the field of fetal CNS anomalies. Due to its multiparametricity and multiplanarity, MRI provides a detailed evaluation of the whole fetal respiratory, gastrointestinal and genitourinary systems, especially on T2-weighted (W) images, with a good tissue contrast resolution. In the evaluation of the digestive tract, T1-W sequences are very important in relation to the typical hyperintensity of the large intestine, due to the presence of meconium. The objective of this review is to focus on the application of fetal MRI in neck, chest and abdominal diseases.

Role of fetal MRI in the evaluation of isolated and non-isolated corpus callosum dysgenesis: results of a cross-sectional study.

PURPOSE: The aims of this study were to characterize isolated and non-isolated forms of corpus callosum dysgenesis (CCD) at fetal magnetic resonance imaging (MRI) and to identify early predictors of associated anomalies. METHODS: We retrospectively analyzed 104 fetuses with CCD undergoing MRI between 2006 and 2016. Corpus callosum, cavum septi pellucidi, biometry, presence of ventriculomegaly, gyration anomalies, cranio-encephalic abnormalities and body malformations were evaluated. Results of genetic tests were also recorded. RESULTS: At MRI, isolated CCD was 26.9%, the rest being associated to other abnormalities. In the isolated group, median gestational age at MRI was lower in complete agenesis than in hypoplasia (22 vs 28 weeks). In the group with additional findings, cortical dysplasia was the most frequently associated feature (P = 0.008), with a more frequent occurrence in complete agenesis (70%) versus other forms; mesial frontal lobes were more often involved than other cortical regions (P = 0.006), with polymicrogyria as the most frequent cortical malformation (40%). Multivariate analysis confirmed the association between complete agenesis and cortical dysplasia (odds ratio = 7.29, 95% confidence interval 1.51-35.21). CONCLUSIONS: CCD is often complicated by other intra-cranial and extra-cranial findings (cortical dysplasias as the most prevalent) that significantly affect the postnatal prognosis. The present study showed CCD with associated anomalies as more frequent than isolated (73.1%). In isolated forms, severe ventriculomegaly was a reliable herald of future appearance of associated features. © 2016 John Wiley & Sons, Ltd.

MRI, US or real-time virtual sonography in the evaluation of adenomyosis?

PURPOSE: Real-time virtual sonography (RVS) allows displaying and synchronizing real-time US and multiplanar reconstruction of MRI images. The purpose of this study was to evaluate the feasibility and ability of RVS to assess adenomyosis since literature shows US itself has a reduced diagnostic accuracy compared to MRI. MATERIALS AND METHODS: This study was conducted over a 4-month period (March-June 2015). We enrolled in the study 52 women with clinical symptoms of dysmenorrhea, methrorragia and infertility. Every patient underwent an endovaginal US examination, followed by a 3T MRI exam and a RVS exam (Hitachi HI Vision Ascendus). The MRI image dataset acquired at the time of the examination was loaded into the fusion system and displayed together with the US images. Both sets of images were then manually synchronized and images were registered using multiple plane MR imaging. Radiologist was asked to report all three examinations separately. RESULTS: On a total of 52 patients, on standard endovaginal US, adenomyosis was detected in 27 cases: of these, 21 presented diffuse adenomyosis, and 6 cases focal form of adenomyosis. MRI detected adenomyosis in 30 cases: 22 of these appeared as diffuse form and 8 as focal form, such as adenomyoma and adenomyotic cyst, thus resulting in 3 misdiagnosed cases on US. RVS confirmed all 22 cases of diffuse adenomyosis and all 8 cases of focal adenomyosis. CONCLUSIONS: Thanks to information from both US and MRI, fusion imaging allows better identification of adenomyosis and could improve the performance of ultrasound operator thus to implement the contribution of TVUS in daily practice.

A prospective study on contrast-enhanced magnetic resonance imaging of testicular lesions: distinctive features of Leydig cell tumours.

OBJECTIVES: Up to 20 % of incidentally found testicular lesions are benign Leydig cell tumours (LCTs). This study evaluates the role of contrast-enhanced magnetic resonance imaging (MRI) in the identification of LCTs in a large prospective cohort study. MATERIALS AND METHODS: We enrolled 44 consecutive patients with at least one solid non-palpable testicular lesion who underwent scrotal MRI. Margins of the lesions, signal intensity and pattern of wash-in and wash-out were analysed by two radiologists. The frequency distribution of malignant and benign MRI features in the different groups was compared by using the chi-squared or Fisher's exact test. Sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy were calculated. RESULTS: The sensitivity of scrotal MRI to diagnose LCTs was 89.47 % with 95.65 % specificity; sensitivity for malignant lesions was 95.65 % with 80.95 % specificity. A markedly hypointense signal on T2-WI, rapid and marked wash-in followed by a prolonged washout were distinctive features significantly associated with LCTs. Malignant lesions were significantly associated with blurred margins, weak hypointense signal on T2-WI ,and weak and progressive wash-in. The overall diagnostic accuracy was 93 %. CONCLUSIONS: LCTs have distinctive contrast-enhanced MRI features that allow the differential diagnosis of incidental testicular lesions. KEY POINTS: • MRI is able to characterize testicular lesions suggesting a specific diagnosis. • Rapid and marked wash-in is a common feature of Leydig cell tumours. • Markedly hypointense T2-WI signal is significantly correlated with benign lesions. • Blurred margins and weak hypointense T2-WI signal are correlated with malignant tumours. • Weak and progressive wash-in features are present in 85 % of seminomatous lesions.

Dandy-Walker Malformation: is the 'tail sign' the key sign?

OBJECTIVE: The study aims to demonstrate the value of the 'tail sign' in the assessment of Dandy-Walker malformation. METHODS: A total of 31 fetal magnetic resonance imaging (MRI), performed before 24 weeks of gestation after second-line ultrasound examination between May 2013 and September 2014, were examined retrospectively. All MRI examinations were performed using a 1.5 Tesla magnet without maternal sedation. RESULTS: Magnetic resonance imaging diagnosed 15/31 cases of Dandy-Walker malformation, 6/31 of vermian partial caudal agenesis, 2/31 of vermian hypoplasia, 4/31 of vermian malrotation, 2/31 of Walker-Warburg syndrome, 1/31 of Blake pouch cyst and 1/31 of rhombencephalosynapsis. All data were compared with fetopsy results, fetal MRI after the 30th week or postnatal MRI; the follow-up depended on the maternal decision to terminate or continue pregnancy. In our review study, we found the presence of the 'tail sign'; this sign was visible only in Dandy-Walker malformation and Walker-Warburg syndrome. CONCLUSION: The 'tail sign' could be helpful in the difficult differential diagnosis between Dandy-Walker, vermian malrotation, vermian hypoplasia and vermian partial agenesis.

Role of magnetic resonance imaging in the prenatal diagnosis of gastrointestinal fetal anomalies.

PURPOSE: This study was done to evaluate the role of fetal magnetic resonance imaging (MRI) in the study of gastrointestinal malformations in comparison to prenatal ultrasound (US). MATERIALS AND METHODS: A prospective (2010-2012) study of 38 fetal MRI scans was performed on 38 fetuses between 24 and 38 weeks of gestation. All the fetuses had a US diagnosis of gastrointestinal anomalies. T2-weighted HASTE, T1-weighted fast gradient echo, TrueFISP and diffusion-weighted images of the fetal abdomen were obtained on a 1.5-Tesla magnet. All fetal MRI diagnoses were compared with postnatal US findings, autopsy or surgical reports. RESULTS: Fetal MRI was able to confirm the sonographic findings in nine of 38 fetuses (23.7%), to provide additional information in 23 of 38 fetuses (60.6%), to exclude the US diagnosis in five cases (5.2%) and to change it in two cases (5.2%). It was not able to characterize a case of gastric duplication and a case of abdominal cystic lymphangioma (5.2%). CONCLUSIONS: Fetal MRI can be used as a complementary imaging modality to US in prenatal evaluation of gastrointestinal anomalies and can be considered a valuable tool not only for confirming or excluding but also for providing additional information to fetal ultrasonographic findings.

May increased CA125 in borderline ovarian tumor be indicative of a poor prognosis? A case report.

We present a case of a 58-year-old menopausal woman referred to our hospital for the presence of large pelvic masses diagnosed by clinical examination and pelvic ultrasound. MRI examination showed voluminous bilateral capsulated multilocular ovarian cysts slightly hyperintense on T1-weighted images with thick septa and small papillary projections. CT scan confirmed the MRI findings. Among the ovarian tumor markers analyzed (CA125, HE4, and CA72.4), only Ca125 was slightly increased (48 U/ml). These data were suggestive of mucinous ovarian tumor. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy, appendectomy, and multiple peritoneal biopsies. Pathological examination revealed bilateral borderline mucinous ovarian tumor with superficial atypical implants. Nine months later, the patient complained of left coxofemoral pain and underwent a PET/TC total body that suggested pubic bone metastases. Ovarian tumor markers were analyzed, and a second PET/TC was performed. CA125 was 252 U/ml, HE4 62 pM/L, and CA72.4 > 100 U/Ml. PET/TC was suggestive of peritoneal carcinosis. The patient was readmitted to the hospital. Clinical examination revealed small vaginal nodules. All nodules were excised. Microscopic analysis of all specimens revealed metastatic mucinous adenocarcinoma of intestinal type.The case shows that even a slight CA125 increase in the presence of a borderline ovarian tumor should not be overlooked since it can be indicative of a progressive disease. This case also highlights its additional diagnostic value when serum CA125 analysis is used in conjunction with MRI and CT imaging for the prognosis of mucinous borderline ovarian tumors (mBOTs).

Role of foetal MRI in the evaluation of ischaemic-haemorrhagic lesions of the foetal brain.

OBJECTIVE: The purpose of this study is to define the role of foetal magnetic resonance imaging (MRI) in evaluating cerebral ischaemic-haemorrhagic lesions and the extension of parenchymal injuries. STUDY DESIGN: From September 2006 to September 2010, 271 foetal MRI have been performed on cases referred to us for ultrasound suspect of brain abnormalities or cytomegalovirus infection and Toxoplasma serum conversion. Foetal MRI was performed with a 1.5-T magnet system without mother sedation. RESULTS: Foetal MRI detected ischaemic-haemorrhagic lesions in 14 of 271 foetuses, consisting of 5% incidence. MRI confirmed the diagnosis in three of 14 cases with ultrasonography (US) suspect of ischaemic-haemorrhagic lesions associated with ventriculomegaly. In one of 14 cases with US findings of cerebellar haemorrhage, MRI confirmed the diagnosis and provided additional information regarding the parenchymal ischaemic injury. In eight of 14 cases with US suspect of ventriculomegaly (3), corpus callosum agenesis (2), hypoplasia of cerebellar vermis (1), holoprosencephaly (1) and spina bifida (1), MRI detected ischaemic and haemorrhagic lesions unidentified at US examination. In two of 14 foetuses with US suspect of intracerebral space-occupying lesion, MRI modified the diagnosis to extra-axial haematoma associated with dural sinus malformation. Results were compared with post-mortem findings or afterbirth imaging follow-up. CONCLUSIONS: Foetal MRI is an additional imaging modality in the diagnosis of cerebral ischemic-haemorrhagic lesions, and it is useful in providing further information on the extension of the parenchymal injury and associated abnormalities, thus improving delivery management.

Pregnancy associated transient osteoporosis of the hip (PR-TOH): A non-obstetric indication to caesarean section. A case report with literature review.

Pregnancy related transient osteoporosis of the hip (PR-TOH) is a rare condition that manifests with sudden pain located in the groin region, anterior thigh and buttocks. It is a benign and in the majority of cases self-limiting disease, related to bone marrow oedema. It occurs during the third trimester of pregnancy or less frequently during the post-partum period. Hip movements are usually restricted by pain and it often becomes a non-obstetric indication for Caesarean delivery. Here, we report a case of unilateral PR-TOH diagnosed by magnetic resonance imaging (MRI) and a literature review.

Incidental diagnosis of a pancreatic adenocarcinoma in a woman affected by gestational diabetes mellitus: case report and literature review.

Pancreatic cancer is rarely diagnosed during pregnancy; it usually manifests with symptoms such as epigastric pain, vomiting, weight loss, and jaundice, rarely mimicking the hemolysis, elevated liver enzymes, and low platelet count syndrome. It has been postulated that there exists a correlation between the diagnosis of gestational diabetes mellitus and the occurrence of pancreatic cancer later in life. We conducted an expert literature review of the 31 available documented pancreatic cancer cases that were diagnosed during pregnancy. We also report pancreatic adenocarcinoma incidentally suspected in an asymptomatic woman affected by gestational diabetes mellitus; the woman was undergoing a fetal growth scan.

GDF5 mutation case report and a systematic review of molecular and clinical spectrum: Expanding current knowledge on genotype-phenotype correlations.

INTRODUCTION: Brachydactyly is a bone development abnormality presenting with variable phenotypes and different transmission patterns. Mutations in GDF5 (Growth and Differentiation Factor 5, MIM *601146) account for a significant amount of cases. Here, we report on a three-generation family, where the proband and the grandfather have an isolated brachydactyly with features of both type A1 (MIM #112500) and type C (MIM #113100), while the mother shows only subtle hand phenotype signs. MATERIALS AND METHODS: Whole Exome Sequencing (WES) was performed on the two affected individuals. An in-depth analysis of GDF5 genotype-phenotype correlations was performed through literature reviewing and retrieving information from several databases to elucidate GDF5-related molecular pathogenic mechanisms. RESULTS: WES analysis disclosed a pathogenic variant in GDF5 (NM_000557.5:c.157dup; NP_000548.2:p.Leu53Profs*41; rs778834209), segregating with the phenotype. The frameshift variant was previously associated with Brachydactyly type C (MIM #113100), in heterozygosity, and with the severe Grebe type chondrodysplasia (MIM #200700), in homozygosity. In-depth analysis of literature and databases allowed to retrieve GDF5 mutations and correlations to phenotypes. We disclosed the association of 49 GDF5 pathogenic mutations with eight phenotypes, with both autosomal dominant and recessive transmission patterns. Clinical presentations ranged from severe defects of limb morphogenesis to mild redundant ossification. We suggest that such clinical gradient can be linked to a continuum of GDF5-activity variation, with loss of GDF5 activity underlying bone development defects, and gain of function causing disorders with excessive bone formation. CONCLUSIONS: Our analysis of GDF5 pathogenicity mechanisms furtherly supports that mutation and zygosity backgrounds resulting in the same level of GDF5 activity may lead to similar phenotypes. This information can aid in interpreting the potential pathogenic effect of new variants and in supporting an appropriate genetic counseling.

Bladder carcinoma: MDCT cystography and virtual cystoscopy.

Bladder carcinoma is the most common tumor among the low urinary tract, accounting for 90% of cancer cases. Conventional cystoscopy represents the gold standard for diagnosis and local management of bladder carcinoma. As the prevalence of transitional cell carcinoma is four-fold greater in men than in women, the endoscopic procedure presents objective difficulties related to the length and bending of male urethra. The most important problems are represented by intense discomfort for the patient and bleeding; furthermore, the high cost, invasivity, and local complications such as infections and mechanical lesions are well-known drawbacks. Additionally, conventional cystoscopy does not provide information about extravescical extensions of the tumor. CT cystography, combined with virtual cystoscopy, is mandatory for TNM staging of the tumor and also is useful when conventional cystoscopy is inconclusive or cannot be performed. We presents the CT cystography findings with virtual endoscopy correlation and bladder carcinoma appearance.

Prenatal whole exome sequencing detects a new homozygous fukutin (FKTN) mutation in a fetus with an ultrasound suspicion of familial Dandy-Walker malformation.

BACKGROUND: Posterior fossa malformations are among the most diagnosed central nervous system (CNS) anomalies detected by ultrasound (US) in prenatal age. We identified the pathogenic gene mutation in a male fetus of 17 weeks of gestation with US suspicion of familial Dandy-Walker spectrum malformation, using Next Generation Sequencing approach in prenatal diagnosis. METHODS: Whole exome sequencing (WES) approach has been performed on fetal genomic DNA. After reads preprocessing, mapping, variant calling, and annotation, a filtering strategy based on allelic frequency, recessive inheritance, and phenotypic ontologies has been applied. A fetal magnetic resonance imaging (MRI) at 18 weeks of gestation has been performed. An in silico analysis of a potential causative missense variant in the fukutin protein has been carried out through a structural modeling approach. RESULTS: We identified a new homozygous missense mutation in fukutin gene (FKTN, NM_006731.2: c.898G>A; NP_006722.2: p.Gly300Arg). Fetal MRI supported molecular findings. Structural modeling analyses indicated a potential pathogenetic mechanism of the variant, through a reduced activation of the sugar moieties, which in turn impairs transfer to dystroglycan and thus its glycosylation. These findings pointed to a redefinition of the US suspicion of recurrence of Dandy-Walker malformation (DWM) to a muscular dystrophy-dystroglycanopathy type A4. CONCLUSIONS: The present case confirmed WES as a reliable tool for the prenatal identification of the molecular bases of early-detected CNS malformations.

Heterozygous nonsense ARX mutation in a family highlights the complexity of clinical and molecular diagnosis in case of chromosomal and single gene disorder co-inheritance.

BACKGROUND: Corpus callosum agenesis (ACC) is one of the most frequent Central Nervous System (CNS) malformations. However, genetics underlying isolated forms is still poorly recognized. Here, we report on two female familial cases with partial ACC. The proband shows isolated partial ACC and a mild neurodevelopmental phenotype. A fetus from a previous interrupted pregnancy exhibited a complex phenotype including partial ACC and the occurrence of a de novo 17q12 microduplication, which was interpreted as probably disease-causing. METHODS: A trio-based clinical exome sequencing (CES) was performed. RESULTS: Clinical exome sequencing data analysis led to identifying a heterozygous nonsense variant (NM_139058.3:c.922G>T; NP_620689.1:p.Glu308Ter) in the aristaless related homeobox gene (ARX) in the proband, with a putative de novo occurrence, producing a hypothetical protein lacking two essential domains. Sanger analysis confirmed the wild-type status of both parents in different tissues, and disclosed the occurrence of the nonsense variant in the fetus of the interrupted pregnancy, suggesting a formerly unrecognized contribution of the ARX mutation to the fetus' phenotype and gonadal or gonadosomatic mosaicism in one of the parents. CONCLUSION: This study describes the phenotype associated with a heterozygous loss of function variant in ARX. Moreover, it highlights the importance of investigating both chromosomal and genetic contributions in cases of complex syndromic phenotypes involving CNS.

Spatiotemporal expansion of primary progenitor zones in the developing human cerebellum.

We present histological and molecular analyses of the developing human cerebellum from 30 days after conception to 9 months after birth. Differences in developmental patterns between humans and mice include spatiotemporal expansion of both ventricular and rhombic lip primary progenitor zones to include subventricular zones containing basal progenitors. The human rhombic lip persists longer through cerebellar development than in the mouse and undergoes morphological changes to form a progenitor pool in the posterior lobule, which is not seen in other organisms, not even in the nonhuman primate the macaque. Disruptions in human rhombic lip development are associated with posterior cerebellar vermis hypoplasia and Dandy-Walker malformation. The presence of these species-specific neural progenitor populations refines our insight into human cerebellar developmental disorders.

Fetal MRI of the central nervous system: State-of-the-art.

Prenatal ultrasonographic (US) examination is considered as the first tool in the assessment of fetal abnormalities. However, several large-scale studies point out that some malformations, in particular central nervous system (CNS) anomalies, are not well characterized through US. Therefore, the actual malformation severity is not always related to prenatal ultrasound (US) findings. Over the past 20 years, ultrafast Magnetic Resonance Imaging (MRI) has progressively increased as a prenatal 3rd level diagnostic technique with a good sensitivity, particularly for the study of fetal CNS malformations. In fact, CNS anomalies are the most common clinical indications for fetal MRI, representing about 80% of the total examinations. This review covers the recent literature on fetal brain MRI, with emphasis on techniques, safety and indications.

Unusual association of SCN2A epileptic encephalopathy with severe cortical dysplasia detected by prenatal MRI.

We present an atypical association of SCN2A epileptic encephalopathy with severe cortical dysplasia. SCN2A mutations are associated with epileptic syndromes from benign to extremely severe in absence of such macroscopic brain findings. Prenatal MRI (Magnetic Resonance Imaging) in a 32 weeks fetus, with US (Ultrasonography) diagnosis of isolated ventriculomegaly showed CNS (Central Nervous System) dysplasia characterized by lack of differentiation between cortical and subcortical layers, pachygyria and corpus callosum dysgenesis. Postnatal MRI confirmed the prenatal findings. On day 6 the baby presented a focal status epilepticus, partially controlled by phenobarbital, phenytoin, and levetiracetam. After three weeks a moderate improvement in seizure control has been achieved with carbamazepine. Exome sequencing detected a de novo heterozygous mutation in the SCN2A gene, encoding the αII-subunit of a sodium channel. The patient findings expand the phenotype spectrum of SCN2A mutations to epileptic encephalopathies with macroscopic brain developmental features.

Diffusion and perfusion quantified by Magnetic Resonance Imaging are markers of human placenta development in normal pregnancy.

PURPOSE: To investigate the potential of bi-exponential model of diffusion-weighted (DW) signal decay to quantify diffusion and perfusion changes in human placenta of normal pregnancies due to its development. METHODS: 26 normal pregnancies at 19-37 weeks of gestation underwent Magnetic Resonance Imaging (MRI) examination at 1.5 T. DW Spin-Echo Echo Planar Imaging with diffusion gradients applied along 3 no-coplanar directions at seven different b-values (0,50,100,150,400,700,1000 s/mm2) was used. Apparent diffusion coefficient (ADC), pseudodiffusion (D*) and perfusion fraction (f) were extracted in selected placenta regions: umbilical (U-ROI), central (C-ROI) and peripheral (P-ROI). The relation between ADC, D*, f and mother age, gestational age (GA), Body-Mass Index (BMI), basal Glycaemia (bG), were evaluated. Pearson correlation with Bonferroni correction was used. RESULTS: A significant negative correlation was found between ADC and GA, for GA≥30w in P-ROI, while no-dependence of ADC on GA was observed in GA range 19-29 weeks. A positive linear correlation was found between f and GA in the C-ROI and between f and GA in P-ROI for GA≥30 week. No significant correlations were found between ADC, D*, f and age, BMI, bG. CONCLUSION: ADC measurements in P-ROI of normal placenta reflects tissue changes occurring in the third trimester of gestation. Specifically, ADC decreases with GA increase. Besides, f increases with the GA increase in the C-ROI and during the third trimester of pregnancy in the P-ROI. These results suggest the potential of diffusion and perfusion parameters extracted by using a biexponential model to provide information about placenta changes during its development.