What Is the Exact Contribution of PITX1 and TBX4 Genes in Clubfoot Development? An Italian Study.

Congenital clubfoot is a common pediatric malformation that affects approximately 0.1% of all births. 80% of the cases appear isolated, while 20% can be secondary or associated with complex syndromes. To date, two genes that appear to play an important role are PTIX1 and TBX4, but their actual impact is still unclear. Our study aimed to evaluate the prevalence of pathogenic variants in PITX1 and TBX4 in Italian patients with idiopathic clubfoot. PITX1 and TBX4 genes were analyzed by sequence and SNP array in 162 patients. We detected only four nucleotide variants in TBX4, predicted to be benign or likely benign. CNV analysis did not reveal duplications or deletions involving both genes and intragenic structural variants. Our data proved that the idiopathic form of congenital clubfoot was rarely associated with mutations and CNVs on PITX1 and TBX4. Although in some patients, the disease was caused by mutations in both genes; they were responsible for only a tiny minority of cases, at least in the Italian population. It was not excluded that other genes belonging to the same TBX4-PITX1 axis were involved, even if genetic complexity at the origin of clubfoot required the involvement of other factors.

High-permittivity pads to enhance SNR and transmit efficiency in MRI of the heart at 7T: a simulation study.

OBJECTIVE: High-permittivity pads have shown promising results in enhancing SNR and transmit efficiency when used for MRI of the brain, but fewer studies have been conducted to examine the performance of high-permittivity pads in other parts of the patient. In this work, we evaluate the impact on SNR and transmit efficiency distributions when high-permittivity pads with different thickness are positioned near the chest of the patient in combination with a transmit/receive array coil. METHODS: The performance of the pads is evaluated through numerical simulations, and both the SNR distribution and the transmit efficiency maps are compared with those obtained when the pads are not present and the distance between the coils and the patient is minimal. The average improvement of SNR and transmit efficiency in the heart is also evaluated for different values of the permittivity of the pads. RESULTS: In the scenario examined, high-permittivity pads can increase SNR and transmit efficiency in the heart volume by as much as 16% and 65%, respectively.

Neuronal activity under transcranial radio-frequency stimulation in metal-free rodent brains in-vivo.

As the use of Radio Frequency (RF) technologies increases, the impact of RF radiation on neurological function continues to receive attention. Whether RF radiation can modulate ongoing neuronal activity by non-thermal mechanisms has been debated for decades. However, the interactions between radiated energy and metal-based neural probes during experimentation could impact neural activity, making interpretation of the results difficult. To address this problem, we modified a miniature 1-photon Ca2+ imaging device to record interference-free neural activity and compared the results to those acquired using metal-containing silicon probes. We monitored the neuronal activity of awake rodent-brains under RF energy exposure (at 950 MHz) and in sham control paradigms. Spiking activity was reliably affected by RF energy in metal containing systems. However, we did not observe neuronal responses using metal-free optical recordings at induced local electric field strengths up to 230 V/m. Our results suggest that RF exposure higher than levels that are allowed by regulatory limits in real-life scenarios do not affect neuronal activity.

Improved whole-brain SNR with an integrated high-permittivity material in a head array at 7T.

PURPOSE: To demonstrate that strategic use of materials with high electric permittivity along with integrated head-sized coil arrays can improve SNR in the entire brain. METHODS: Numerical simulations were used to design a high-permittivity material (HPM) helmet for enhancing SNR throughout the brain in receive arrays of 8 and 28 channels. Then, two 30-channel head coils of identical geometry were constructed: one fitted with a prototype helmet-shaped ceramic HPM helmet, and the second with a helmet-shaped low-permittivity shell, each 8-mm thick. An eight-channel dipole array was used for excitation. In vivo maps of excitation flip angle and SNR were acquired. RESULTS: Simulation results showed improvement in transmit efficiency by up to 65% and in receive-side SNR by up to 47% on average through the head with use of an HPM helmet. Experimental results showed that experimental transmit efficiency was improved by approximately 56% at the center of brain, and experimental receive-side SNR (SNR normalized to flip angle) was improved by approximately 21% on average through orthogonal planes through the cerebrum, including at the center of the brain, with the HPM. CONCLUSION: Although HPM is used increasingly to improve transmit efficiency locally in situations in which the transmit coil and imaging volume are much larger than the HPM, here we demonstrate that HPM can also be used to improve transmit efficiency and receive-side SNR throughout the brain by improving performance of a head-sized receive array. This includes the center of the brain, where it is difficult to improve SNR by other means.

Temperature-based MRI safety simulations with a limited number of tissues.

PURPOSE: Demonstrate ability to produce reasonable simulations of temperature using numerical models of the human body with a limited number of tissues. METHODS: For both a male and female human body model, numerical simulations were used to calculate temperature distributions in three different models of the same human body: the original model with 35 tissues for the male model and 76 tissues for the female model, a simplified model having only three tissues (muscle, fat, and lung), and a simplified model having six tissues (muscle, fat, lung, bone, brain, and skin). RESULTS: Although a three-tissue model gave reasonable specific absorption rate estimates in comparison to an original with many more tissues, because of tissue-specific thermal and physiological properties that do not affect specific absorption rate, such as rate of perfusion by blood, the three-tissue model did not provide temperature distributions similar to those of the original model. Inclusion of a few additional tissues, as in the six-tissue model, produced results in much better agreement with those from the original model. CONCLUSION: Reasonable estimates of temperature can be simulated with a limited number of tissues, although this number is higher than the number of tissues required to produce reasonable simulations of specific absorption rate. For exposures primarily in the head and thorax, six tissues may be adequate for reasonable estimates of temperature.

Optimization of the order and spacing of sequences in an MRI exam to reduce the maximum temperature and thermal dose.

PURPOSE: Evaluate the possibility to reduce specific energy absorption rate (SAR)-induced maximum temperature and thermal dose by rearranging the order and spacing of sequences without increasing duration of the MRI examination. METHODS: Using numerical simulations based on an actual SAR-intensive MRI examination, optimizations to reduce either maximum temperature or thermal dose were performed. For each permutation of groups of sequences having the same patient table position, temperature and thermal dose were computed very rapidly using recently published methods. Disposition of sequences was further adjusted by optimizing the spacing between each sequence without exceeding the original exam duration. RESULTS: The maximum simulated temperature in the original exam was 42.38°C, and the maximum thermal dose was 3.23 cumulative effective minutes at 43°C (CEM43). After optimization to reduce maximum temperature, it was 41.77°C, and after optimization to minimize the thermal dose, it was 1.42 CEM43. CONCLUSION: It is possible to reduce maximum temperature and thermal dose in the exam by changing the arrangement and spacing of the sequences without increasing the duration of the exam (by increasing TR or adding delays) or compromising image quality (by reducing flip angles).

Parallel transmission RF pulse design with strict temperature constraints.

RF safety in parallel transmission (pTx) is generally ensured by imposing specific absorption rate (SAR) limits during pTx RF pulse design. There is increasing interest in using temperature to ensure safety in MRI. In this work, we present a local temperature correlation matrix formalism and apply it to impose strict constraints on maximum absolute temperature in pTx RF pulse design for head and hip regions. Electromagnetic field simulations were performed on the head and hip of virtual body models. Temperature correlation matrices were calculated for four different exposure durations ranging between 6 and 24 min using simulated fields and body-specific constants. Parallel transmission RF pulses were designed using either SAR or temperature constraints, and compared with each other and unconstrained RF pulse design in terms of excitation fidelity and safety. The use of temperature correlation matrices resulted in better excitation fidelity compared with the use of SAR in parallel transmission RF pulse design (for the 6 min exposure period, 8.8% versus 21.0% for the head and 28.0% versus 32.2% for the hip region). As RF exposure duration increases (from 6 min to 24 min), the benefit of using temperature correlation matrices on RF pulse design diminishes. However, the safety of the subject is always guaranteed (the maximum temperature was equal to 39°C). This trend was observed in both head and hip regions, where the perfusion rates are very different.

On the potential for RF heating in MRI to affect metabolic rates and 18 FDG signal in PET/MR: simulations of long-duration, maximum normal mode heating.

PURPOSE: To examine the possibility that MR-induced RF power deposition (SAR) and the resulting effects on temperature-dependent metabolic rates or perfusion rates might affect observed 18FDG signal in PET/MR. METHODS: Using numerical simulations of the SAR, consequent temperature increase, effect on rates of metabolism or perfusion, and [18FDG] throughout the body, we simulated the potential effect of maximum-allowable whole-body SAR for the entire duration of an hour-long PET/MR scan on observed PET signal for two different 18FDG injection times: one hour before onset of imaging and concurrent with the beginning of imaging. This was all repeated three times with the head, the heart, and the abdomen (kidneys) at the center of the RF coil. RESULTS: Qualitatively, little effect of MR-induced heating is observed on simulated PET images. Maximum relative increases in PET signal (26% and 31% increase, respectively, for the uptake models based on metabolism and the perfusion) occur in regions of low baseline metabolic rate (also associated with low perfusion and, thus, greater potential temperature increase due to high local SAR), such that PET signal in these areas remains comparatively low. Maximum relative increases in regions of high metabolic rate (and also high perfusion: heart, thyroid, brain, etc.) are affected mostly by the relatively small increase in core body temperature and thus are not affected greatly (10% maximum increase). CONCLUSIONS: Even for worst-case heating, little effect of MR-induced heating is expected on 18FDG PET images during PET/MR for many clinically relevant applications. For quantitative, dynamic MR/PET studies requiring high SAR for extended periods, it is hoped that methods like those introduced here can help account for such potential effects in design of a given study, including selection of reference locations that should not experience notable increase in temperature.

Effects of Anatomical Differences on Electromagnetic Fields, SAR, and Temperature Change.

Electromagnetic field simulations are increasingly used to assure RF safety of patients during MRI exams. In practice, however, tissue property distribution of the patient being imaged is not known, but may be represented with a pre-existing model. Repeatedly, agreement in transmit magnetic (B1+) field distributions between two geometries has been used to suggest agreement in heating distributions. Here we examine relative effects of anatomical differences on B1+ distribution, Specific Absorption Rate (SAR) and temperature change (ΔT). Numerical simulations were performed for a single surface coil positioned adjacent a homogeneous phantom and bovine phantom, each with slight geometric variations, and adjacent two different human body models. Experimental demonstration was performed on a bovine phantom using MR thermometry and B1+ mapping. Simulations and experiments demonstrate that B1+ distributions in different samples can be well correlated, while notable difference in maximum SAR and ΔT occur. This work illustrates challenges associated with utilizing simulations or experiments for RF safety assurance purposes. Reliance on B1+ distributions alone for validation of simulations and/or experiments with a sample or subject for assurance of safety in another should be performed with caution.

Predicting long-term temperature increase for time-dependent SAR levels with a single short-term temperature response.

PURPOSE: Present a novel method for rapid prediction of temperature in vivo for a series of pulse sequences with differing levels and distributions of specific energy absorption rate (SAR). THEORY AND METHODS: After the temperature response to a brief period of heating is characterized, a rapid estimate of temperature during a series of periods at different heating levels is made using a linear heat equation and impulse-response (IR) concepts. Here the initial characterization and long-term prediction for a complete spine exam are made with the Pennes' bioheat equation where, at first, core body temperature is allowed to increase and local perfusion is not. Then corrections through time allowing variation in local perfusion are introduced. RESULTS: The fast IR-based method predicted maximum temperature increase within 1% of that with a full finite difference simulation, but required less than 3.5% of the computation time. Even higher accelerations are possible depending on the time step size chosen, with loss in temporal resolution. Correction for temperature-dependent perfusion requires negligible additional time and can be adjusted to be more or less conservative than the corresponding finite difference simulation. CONCLUSION: With appropriate methods, it is possible to rapidly predict temperature increase throughout the body for actual MR examinations.

[Early attachement relationships and epigenetic customization]. / La regolazione epigenetica della relazione primaria.

Recently, new findings in epigenetic science switched the focus from the observation of physiological intragenomic dynamics to the idea of an environmental co-construction of phenotypic expression. In psichodynamic field, objectual relations and attachement theoreticians emphasized the interpersonal dimension of individual development, focusing the attention on the relational matrix of self organization. The construction of stable affective-behavioral traits throughout different parenting styles has actually found a coincidence in ethological studies, which have explored the epigenetic processes underlying the relationship between caregiving and HPA stress responsiveness. An adequate parenting style seems to support affective regulation throughout psychobiological hidden moderators, which would tend to rebalance the physiological systems homeostasis; an unconfident attachment style would promote, on the other hand, the allostatic load rise. Sites of longlife epigenetic susceptibility have also been identified in humans; although associated with risk of maladaptive developing in adverse environmental conditions, they seem to confer protection under favorable conditions. This persisting possibility of reorganization of stable traits throughout lifetime, which seems to be activated by a relevant environmental input, grant to significant relationships, and to therapeutical one as well, an implicit reconditioning potential which could result into the configuration of new stable affective-behavioral styles.

[Perinatal depression and affective bonds: experience in close relationship during pregnancy]. / Depressione perinatale e relazioni affettive: l'experience in close relationship in gravidanza.

AIM: This study aims to investigate the influence of the "romantic attachment" style, stressful life events, social factors on the risk of developing a depression during pregnancy and on the severity of depressive symptoms. METHODS: The study started with a screening on a sample of 453 women, during their third trimester of pregnancy, to which has been administered a survey data form, the Edinburgh Postnatal Depression Scale (EPDS) and the Experience in Close Relationship (ECR). Based on the results at EPDS, a clinical group of pre-natal depression (D=89) was selected and compared with a control group (C=89), in regards to psychopathological and social variables, exposure to stressful life events and attachment patterns. Analysis of correlation were performed to evaluate the influence of these factors on depressive symptoms severity. RESULTS: In D group, 52.8% of subjects reported previous psychiatric disorders and 49.4% a familiarity; 29.2% of these women complains of conflicts with their family of origin and 32.6% with partner. The ECR showed a prevalence of "fearful-avoidant" attachment style in clinical group (29.2% vs 1.1%, p=0.000); besides, ECR dimensions ("Avoidance", "Anxiety"), correlate with the severity of depressive symptoms. CONCLUSIONS: Positive family history for psychiatric disorders and an insecure romantic attachment might influence the development and the severity of perinatal depression.

Perinatal Depression and Patterns of Attachment: A Critical Risk Factor?

Background. This study aims to verify if the presence and severity of perinatal depression are related to any particular pattern of attachment. Methods. The study started with a screening of a sample of 453 women in their third trimester of pregnancy, who were administered a survey data form, the Edinburgh Postnatal Depression Scale (EPDS) and the Experience in Close Relationship (ECR). A clinical group of subjects with perinatal depression (PND, 89 subjects) was selected and compared with a control group (C), regarding psychopathological variables and attachment patterns. Results. The ECR showed a prevalence of "Fearful-Avoidant" attachment style in PND group (29.2% versus 1.1%, p < 0.001); additionally, the EPDS average score increases with the increasing of ECR dimensions (Avoidance and Anxiety). Conclusion. The severity of depression increases proportionally to attachment disorganization; therefore, we consider attachment as both an important risk factor as well as a focus for early psychotherapeutic intervention.

Consideration of the effects of intense tissue heating on the RF electromagnetic fields during MRI: simulations for MRgFUS in the hip.

Due to the strong dependence of tissue electrical properties on temperature, it is important to consider the potential effects of intense tissue heating on the RF electromagnetic fields during MRI, as can occur in MR-guided focused ultrasound surgery. In principle, changes of the RF electromagnetic fields could affect both efficacy of RF pulses, and the MRI-induced RF heating (SAR) pattern. In this study, the equilibrium temperature distribution in a whole-body model with 2 mm resolution before and during intense tissue heating up to 60 °C at the target region was calculated. Temperature-dependent electric properties of tissues were assigned to the model to establish a temperature-dependent electromagnetic whole-body model in a 3T MRI system. The results showed maximum changes in conductivity, permittivity, [absolute value]B(1)(+)[absolute value] and SAR of about 25%, 6%, 2%, and 20%, respectively. Though the B1 field and SAR distributions are both temperature-dependent, the potential harm to patients due to higher SARs is expected to be minimal and the effects on the B1 field distribution should have minimal effect on images from basic MRI sequences.

[Coffee consumption in depressive disorders: it's not one size fits all]. / Consumo di caffè nei disturbi depressivi: una dose giusta, non per tutti.

Caffeine is considered the world's most popular psychoactive substance. Its actions on the central nervous system, mainly mediated by antagonism of adenosine receptors and subsequent modulation of dopaminergic activity, would be particularly sought by depressed patients, as an attempt of self-medication. However, published data suggested that coffee consumption may worsen psychopathological conditions in mood disorders. Thus, we reviewed available evidence in the literature that investigated the effects of coffee consumption on clinical development of underlying psychopathology. Literature research was done by typing on Medline/PubMed and PsychINFO the key words "coffee AND major depression", "coffee AND dysthymia". The research was limited to English language publications and to studies conducted exclusively on humans. Although literature data are conflicting, extensive follow-up studies indicate a significant caffeine effect on risk reduction of developing clinical depression symptoms. Clinical worsening was observed mainly in cases of postpartum depression and comorbid panic disorder. Taking in account the study limitations, we observed a biphasic profile in caffeine psychostimulant effect: low to moderate doses may correlate with a reduction in depressive risk in healthy subjects and an improvement of many clinical symptoms (attention, arousal, psychomotor performance) in depressed patients, whereas the assumption of high doses may result in thymic dysregulation, favor mixed affective states and worsen circadian profiles and anxiety symptoms.

Measurement of SAR-induced temperature increase in a phantom and in vivo with comparison to numerical simulation.

PURPOSE: To compare numerically simulated and experimentally measured temperature increase due to specific energy absorption rate from radiofrequency fields. METHODS: Temperature increase induced in both a phantom and in the human forearm when driving an adjacent circular surface coil was mapped using the proton resonance frequency shift technique of magnetic resonance thermography. The phantom and forearm were also modeled from magnetic resonance image data, and both specific energy absorption rate and temperature change as induced by the same coil were simulated numerically. RESULTS: The simulated and measured temperature increase distributions were generally in good agreement for the phantom. The relative distributions for the human forearm were very similar, with the simulations giving maximum temperature increase about 25% higher than measured. CONCLUSION: Although a number of parameters and uncertainties are involved, it should be possible to use numerical simulations to produce reasonably accurate and conservative estimates of temperature distribution to ensure safety in magnetic resonance imaging. R01 EB006563

A fast, analytically based method to optimize local transmit efficiency for a transmit array.

PURPOSE: To develop an analytically based algorithm for rapid optimization of the local radiofrequency magnetic (B1+) field intensity for a given radiofrequency power through a transmit array. The analytical nature of the method will yield insight to optimization requirements and provides a valuable reference for numerically based searches. METHODS: With the knowledge of the B1+ field distribution generated by each single coil of the array, both the phases and the amplitudes of each coil current are optimized to maximize the magnitude of the B1+ field in a specific location of the body per unit of power transmitted through the array and, consequently, minimizing the whole body specific absorption rate for a given pulse sequence. RESULTS: Simulations considering the human body show that the proposed method can reduce the whole-body specific absorption rate for a given B1+ magnitude at the location of interest by a factor of about 6.3 compared to the classic birdcage current configuration, and by a factor of 3.2 compared to phase-only shimming in a case with significant coupling between the elements of the array. CONCLUSION: The proposed method can rapidly provide valuable information pertinent to the optimization of field distributions from transmit arrays.

An approach to rapid calculation of temperature change in tissue using spatial filters to approximate effects of thermal conduction.

We present an approach to performing rapid calculations of temperature within tissue by interleaving, at regular time intervals, 1) an analytical solution to the Pennes (or other desired) bioheat equation excluding the term for thermal conduction and 2) application of a spatial filter to approximate the effects of thermal conduction. Here, the basic approach is presented with attention to filter design. The method is applied to a few different cases relevant to magnetic resonance imaging, and results are compared to those from a full finite-difference (FD) implementation of the Pennes bioheat equation. It is seen that results of the proposed method are in reasonable agreement with those of the FD approach, with about 15% difference in the calculated maximum temperature increase, but are calculated in a fraction of the time, requiring less than 2% of the calculation time for the FD approach in the cases evaluated.

Radiofrequency field enhancement with high dielectric constant (HDC) pads in a receive array coil at 3.0T.

PURPOSE: To investigate the use of a new high-dielectric constant (HDC) material for improving SNR and transmission efficiency for clinical MRI applications at 3 Tesla (T) with cervical spine imaging. MATERIALS AND METHODS: Human subjects were imaged using a commercial cervical spine receive array coil on a clinical system with and without pads containing Barium Titanate beads in deuterium water placed around the neck. Numerical electromagnetic field simulations of the same configuration were also performed. RESULTS: Experimental and simulated maps of transmit and receive fields showed greater efficiency for imaging the cervical spine when the pads were present. Experimental measurements showed a significant improvement in SNR with the pads present and an average input power reduction of 46%. CONCLUSION: Use of HDC material can enhance SNR and transmission efficiency for clinical imaging of the cervical spine at 3.0T.

[Parental care and post partum depression: a case report]. / Cure parentali e depressione post partum: un caso clinico.

The post partum depression (PPD) is a severe risk factor for the emotional and cognitive development of offspring. The Authors describe the relationship between mother with PPD and her two-year old child. The mother repeats patterns of parental care experienced during her own childhood.