Estimation of radiation dose and establishment of local diagnostic reference levels for computed tomography of head in pediatric population.

BACKGROUND: Pediatric population is more sensitive to the effects of radiation than adults. Establishing diagnostic reference level (DRL) is an efficient dose optimization technique implemented by many countries for reducing radiation dose during Computed Tomography (CT) examinations. OBJECTIVES: To estimate radiation dose and establish a new local diagnostic reference level for CT head examination in the pediatric population. MATERIALS AND METHODS: We prospectively recruited 143 pediatric patients referred for CT head examination with age ranging from 0-5 years old. All patients had undergone CT head examination using the standard pediatric head protocol. Volumetric CT dose index (CTDIvol) and dose length product (DLP) were recorded. The effective dose was first calculated. Then, 75th percentile of dose indices was calculated to establish DRLs. RESULTS: DRLs in terms of CTDIvol and DLP are 23.84 mGy, 555.99 mGy.cm for patients <1 years old and 28.65 mGy, 794.99 mGy.cm for patients from 1-5 years old, respectively. Mean effective doses for <1 years old patients and 1-5 years old patients are 2.91 mSv and 2.78 mSv respectively. CONCLUSION: The study concludes that DRL in terms of CTDIvol is lower but DRL in terms of DLP and the effective dose is higher compared to a few other studies which necessitate the need for dose optimization.

Genetic disorders with central nervous system white matter abnormalities: An update.

Several genetic disorders have variable degree of central nervous system white matter abnormalities. We retrieved and reviewed 422 genetic conditions with prominent and consistent involvement of white matter from the literature. We herein describe the current definitions, classification systems, clinical spectrum, neuroimaging findings, genomics, and molecular mechanisms of these conditions. Though diagnosis for most of these disorders relies mainly on genomic tests, specifically exome sequencing, we collate several clinical and neuroimaging findings still relevant in diagnosis of clinically recognizable disorders. We also review the current understanding of pathophysiology and therapeutics of these disorders.

Bi-allelic missense variant, p.Ser35Leu in EXOSC1 is associated with pontocerebellar hypoplasia.

RNA exosome is a highly conserved ribonuclease complex essential for RNA processing and degradation. Bi-allelic variants in exosome subunits EXOSC3, EXOSC8 and EXOSC9 have been reported to cause pontocerebellar hypoplasia type 1B, type 1C and type 1D, respectively, while those in EXOSC2 cause short stature, hearing loss, retinitis pigmentosa and distinctive facies. We ascertained an 8-months-old male with developmental delay, microcephaly, subtle dysmorphism and hypotonia. Pontocerebellar hypoplasia and delayed myelination were noted on neuroimaging. A similarly affected elder sibling succumbed at the age of 4-years 6-months. Chromosomal microarray returned normal results. Exome sequencing revealed a homozygous missense variant, c.104C > T p.(Ser35Leu) in EXOSC1 (NM_016046.5) as the possible candidate. In silico mutagenesis revealed loss of a polar contact with neighboring Leu37 residue. Quantitative real-time PCR indicated no appreciable differences in EXOSC1 transcript levels. Immunoblotting and blue native PAGE revealed reduction in the EXOSC1 protein levels and EXO9 complex in the proband, respectively. We herein report an individual with the bi-allelic variant c.104C>T p.(Ser35Leu) in EXOSC1 and clinical features of pontocerebellar hypoplasia type 1. Immunoblotting and blue native PAGE provide evidence for the pathogenicity of the variant. Thus, we propose EXOSC1 as a novel candidate gene for pontocerebellar hypoplasia.

Biallelic start loss variant, c.1A > G in GCSH is associated with variant nonketotic hyperglycinemia.

The glycine cleavage system H protein (GCSH) is an integral part of the glycine cleavage system with its additional involvement in the synthesis and transport of lipoic acid. We hypothesize that pathogenic variants in GCSH can cause variant nonketotic hyperglycinemia (NKH), a heterogeneous group of disorders with findings resembling a combination of severe NKH (elevated levels of glycine in plasma and CSF, progressive lethargy, seizures, severe hypotonia, no developmental progress, early death) and mitochondriopathies (lactic acidosis, leukoencephalopathy and Leigh-like lesions on MRI). We herein report three individuals from two unrelated Indian families with clinical, biochemical, and radiological findings of variant NKH, harboring a biallelic start loss variant, c.1A > G in GCSH.

Clinical and genetic spectrum of 104 Indian families with central nervous system white matter abnormalities.

Genetic disorders with predominant central nervous system white matter abnormalities (CNS WMAs), also called leukodystrophies, are heterogeneous entities. We ascertained 117 individuals with CNS WMAs from 104 unrelated families. Targeted genetic testing was carried out in 16 families and 13 of them received a diagnosis. Chromosomal microarray (CMA) was performed for three families and one received a diagnosis. Mendeliome sequencing was used for testing 11 families and all received a diagnosis. Whole exome sequencing (WES) was performed in 80 families and was diagnostic in 52 (65%). Singleton WES was diagnostic for 50/75 (66.67%) families. Overall, genetic diagnoses were obtained in 77 families (74.03%). Twenty-two of 47 distinct disorders observed in this cohort have not been reported in Indian individuals previously. Notably, disorders of nuclear mitochondrial pathology were most frequent (9 disorders in 20 families). Thirty-seven of 75 (49.33%) disease-causing variants are novel. To sum up, the present cohort describes the phenotypic and genotypic spectrum of genetic disorders with CNS WMAs in our population. It demonstrates WES, especially singleton WES, as an efficient tool in the diagnosis of these heterogeneous entities. It also highlights possible founder events and recurrent disease-causing variants in our population and their implications on the testing strategy.

Pulmonary aspergilloma on transthoracic ultrasound.

PURPOSE: Pulmonary aspergilloma affects immunocompromised patients but is also a recurrent condition in patients previously treated for pulmonary tuberculosis. METHODS AND RESULTS: We report the case of a 45-year-old patient with a history of cured pulmonary tuberculosis 15 years earlier in whom we visualized pulmonary aspergilloma by transthoracic lung sonography. Sonography of pulmonary aspergilloma demonstrated an oval cavity with hypoechoic contents and an irregular border, measuring a diameter of 4.7 cm; inside the lesion, a roundish structure with an anechoic rim was discernable. CONCLUSIONS: The sonographic findings corresponded to chest X-ray and computed tomography imaging in this patient and to previously reported sonographic characteristics of mycotic abscesses in other organs. Lung ultrasound may be a tool to identify pulmonary aspergilloma, especially as a point-of-care imaging tool and where other imaging modalities are inaccessible.

Novel variant p.(Ala102Thr) in SDHB causes mitochondrial complex II deficiency: Case report and review of the literature.

Leigh syndrome is a clinically and radiologically heterogeneous condition with approximately 75 genes, nuclear and mitochondrial, known to be implicated in its pathogenesis. Leigh syndrome due to complex II deficiency constitutes 2% to 7% of these cases. Previously, nine individuals with Leigh syndrome have been reported with pathogenic variants in SDHB, which encodes for the iron-sulfur cluster subunit of mitochondrial respiratory chain complex II. The proband presented with Leigh syndrome. Exome sequencing revealed a homozygous missense variant p.(Ala102Thr) in SDHB. In silico protein modeling of the wild-type and mutant proteins showed potentially decreased protein stability. We hereby report another individual with Leigh syndrome due to SDHB-related mitochondrial complex II deficiency and review the phenotype and genotype associated with this condition.

Intra-articular steroid for adhesive capsulitis: does hydrodilatation give any additional benefit? A randomized control trial.

OBJECTIVES: To assess the benefit offered by capsular hydrodilatation in addition to intra-articular steroid injections in cases of adhesive capsulitis, assess outcomes in diabetic patients with capsular hydrodilatation as compared to non-diabetics and correlate duration of symptoms with outcome based on the type of intervention given. MATERIALS AND METHODS: This prospective double-blinded randomized control trial included patients presenting with clinical features of adhesive capsulitis with no evidence of rotator cuff pathology and randomized them into two groups-intra-articular steroid with hydrodilatation (distension group) and only intra-articular steroid (non-distension group) with intervention being performed as per the group allotted. Primary outcome measure was Shoulder Pain and Disability Index (SPADI) scores which were taken pre-intervention, at 1.5, 3 and 6 months post-intervention, which were assessed by generalized linear model statistics and Pearson correlation. RESULTS: Although there was statistically significant drop in SPADI in both groups over time [F(1.9, 137.6) = 112.2; p < 0.001], mean difference in SPADI between the 2 groups was not statistically significant (1.53; CI:-3.7 to 6.8; p = 0.56). There was no significant difference between both groups among diabetics [F(1,38) = 0.04; p = 0.95] and no significant difference between diabetic and non-diabetic patients who received hydrodilatation [F(1.8, 60) = 2.26; p = 0.12]. There was no significant correlation between the reduction in SPADI scores and duration of symptoms in any subset of the study population. CONCLUSION: Shoulder joint hydrodilatation offered no additional benefit compared to intra-articular steroid injections for shoulder adhesive capsulitis. Outcome for diabetics and non-diabetics were similar and there was no correlation between duration of symptoms and outcome.

Homozygous p.(Glu87Lys) variant in ISCA1 is associated with a multiple mitochondrial dysfunctions syndrome.

The iron-sulfur (Fe-S) cluster (ISC) biogenesis pathway is indispensable for many fundamental biological processes and pathogenic variations in genes encoding several components of the Fe-S biogenesis machinery, such as NFU1, BOLA3, IBA57 and ISCA2 are already implicated in causing four types of multiple mitochondrial dysfunctions syndromes (MMDS). We report on two unrelated families, with two affected children each with early onset neurological deterioration, seizures, extensive white matter abnormalities, cortical migrational abnormalities, lactic acidosis and early demise. Exome sequencing of two affected individuals, one from each family, revealed a homozygous c.259G>A [p.(Glu87Lys)] variant in ISCA1 and Mendelian segregation was confirmed in both families. The ISCA1 variant lies in the only shared region of homozygosity between the two families suggesting the possibility of a founder effect. In silico functional analyses and structural modeling of the protein predict the identified ISCA1 variant to be detrimental to protein stability and function. Notably the phenotype observed in all affected subjects with the ISCA1 pathogenic variant is similar to that previously described in all four types of MMDS. Our findings suggest association of a pathogenic variant in ISCA1 with another MMDS.

Accuracy of Whole-Body DWI for Metastases Screening in a Diverse Group of Malignancies: Comparison With Conventional Cross-Sectional Imaging and Nuclear Scintigraphy.

OBJECTIVE: The purpose of this study is to assess the role of whole-body (WB) DWI as a screening modality for the detection of metastases and to compare it to conventional cross-sectional imaging modalities or nuclear scintigraphy in a population with various histopathologic malignancies. SUBJECTS AND METHODS: WB DWI and conventional imaging (CT, MRI, or scintigraphy) were performed for patients with known malignancies for metastatic workup, and these patients were followed up for a period of 1 year. Two radiologists assessed WB DW images separately, and conventional images were assessed by the senior radiologist. The metastatic lesions were classified into four regions: liver, lung, skeletal system, and lymph nodes. The reference standard was considered on the basis of histopathologic confirmation or clinical follow-up of the metastatic lesions. RESULTS: WB DWI was slightly inferior to conventional imaging modalities for the detection of hepatic metastases (sensitivity, 86.6% vs 93.3%; specificity, 91.6% vs 95.8%; and accuracy, 89.7% vs 94.8%) and skeletal metastases (sensitivity, 81.8% vs 89.4%; specificity, 86.4% vs 94.3%; and accuracy, 85.2% vs 93.0%); however, the differences were not statistically significant (p = 0.625 for hepatic metastases and p = 0.0953 for skeletal metastases, McNemar test). WB DWI was statistically significantly inferior to conventional imaging for the detection of lymph node metastases (sensitivity, 74.0% vs 81.5%; specificity, 87.9% vs 90.1%; accuracy, 81.4% vs 86.0%; p = 0.0389). WB DWI was statistically significantly inferior to conventional imaging for the detection of pulmonary metastases (sensitivity, 33.3% vs 100.0%; specificity, 90.9% vs 100.0%; accuracy, 60.8% vs 100.0%; p = 0.045). CONCLUSION: WB DWI can be used for screening hepatic and skeletal metastases, but its reliability as the sole imaging sequence for the detection of lymph nodal and pulmonary metastases is poor and, at present, it cannot replace conventional imaging modalities.

Phenotypic variability in patients with interstitial 6q21-q22 microdeletion and Acro-Cardio-Facial syndrome.

Deletions of 6q are known to be associated with variable clinical phenotypes including facial dysmorphism, hand malformations, heart defects, microcephaly, intellectual disability, epilepsy, and other neurodevelopmental and neuropsychiatric conditions. Here, we report a 7-year-old boy evaluated for facial dysmorphism, trigonocephaly, microcephaly, global developmental delay, and behavioral abnormalities. Molecular karyotyping revealed a 13-Mb deletion within 6q21-q22.31, (chr6:105,771,520-119,130,805; hg19, GRch37) comprising 81 genes. Review of 15 cases with interstitial 6q21-q22.3 deletion from the literature showed that facial dysmorphism, intellectual disability, and corpus callosum abnormalities are the most consistent clinical features in these individuals. Deleted genes and breakpoints in the 6q21-q22 region of the patient reported here are similar to two earlier reported cases with the clinical diagnosis of Acro-Cardio-Facial syndrome. However, the present case lacks characteristic clinical findings of Acro-Cardio-Facial syndrome. We discuss, the considerable phenotypic variability seen in individuals with 6q21-q22 microdeletion and emphasize the need for further scrutiny into the hypothesis of Acro-Cardio-Facial syndrome being a microdeletion syndrome. © 2016 Wiley Periodicals, Inc.

Rare Presentation of Pseudomyxoma Retroperitonei: Stretching the Limits.

A 55-year-old woman presented with a mucopurulent sinusal discharge from the right supragluteal region, with symptoms over the previous five months. This abscess began as a slowly swelling growth, which eventually turned into a discharging sinus, and she was diagnosed with a gluteal abscess. The patient underwent incisional drainage, and intra-operatively, the sinus tract could be seen extending to the retroperitoneum. A subsequent CT scan and an MRI of the abdomen revealed a large heterogeneous retroperitoneal cystic mass on the right side of midline, extending inferiorly into the anterior thigh along the iliopsoas. Superiorly, a tubular projection extended from the lesion, indenting the ileocaecal junction, while a fluid filled cutaneous fistulous tract was seen, extending to the right flank. A diagnosis of pseudomyxoma retroperitonei, likely of retrocaecal appendicular origin, was proposed. An explorative laparotomy with an appendectomy, and the evacuation of the retroperitoneal collection were completed. The subsequent histopathology confirmed the diagnosis of appendicular mucinous cystadenoma, with pseudomyxoma retroperitonei.

Clinical utility of fetal autopsy and its impact on genetic counseling.

OBJECTIVES: We aimed to analyze the utility of fetal autopsy in terms of its contribution to establishing a definitive diagnosis and its impact on genetic counseling. SUBJECTS AND METHODS: Detailed fetal autopsy was carried out in fetuses referred for examination. Clinical utility of fetal autopsy and its impact on counseling were measured by adapting previously published parameters. RESULTS: We performed autopsy in 230 fetuses. There were 106 cases with single system and 92 cases with multisystem involvement. We confirmed prenatal findings in 23% of cases and observed additional findings in 37% of cases. In 23% of cases, autopsy findings differed enough to change the diagnosis. However, in 17% of fetuses, no cause of fetal loss was determined. Risk of recurrence became clear in 30.3% of the fetuses, and risk remained the same, but the diagnosis was different in 4.8% of cases after autopsy. Hence, autopsy led to refinement of the risk of recurrence in 36% of cases. Autopsy aided prenatal counseling of couples in 77% of cases by either confirming the prenatal findings (35%) or providing new information/ruling out a diagnosis (42%). CONCLUSION: The present study quantifies the utility of fetal autopsy in reproductive genetic counseling in a large cohort.

Fetal akinesia deformation sequence: expanding the phenotypic spectrum.

We report on two unrelated fetuses born to nonconsanguineous couples with fetal akinesia deformation sequence (FADS). The fetuses shared facial features, micrognathia, fetal finger pads, bulbous digital tips, pterygia, clubfeet, ventriculomegaly, and cerebellar anomalies. Both had loss/absence of Purkinje cells in cerebellum. The first family had a similarly affected previous pregnancy suggesting an autosomal recessive inheritance. The second fetus, in addition to the findings in the first, had cleft palate and defective lobulation of lungs. These fetuses appear to have the Pena-Shokeir phenotype (PSP) or FADS. These two cases seem to define a newly recognizable subtype of FADS with bulbous digital tips, prominent digit pads and cerebellar anomalies, and highlight the phenotypic diversity of syndromes with multiple congenital contractures manifesting in utero.

Doppler evaluation of ocular vessels in patients with primary open angle glaucoma.

PURPOSE: To assess ocular blood flow in patients with primary open angle glaucoma (POAG) with or without progressive visual field loss in comparison with controls. METHODS: Color Doppler imaging was performed on 78 eyes with established POAG (25 with progressive visual field loss and 53 with stable visual field) and 78 control eyes. Peak systolic velocity, end diastolic velocity (EDV), and resistance index (RI) were measured in the ophthalmic (OA), central-retinal, and medial and lateral posterior ciliary arteries. RESULTS: Peak systolic velocity and EDV were lower and RI was higher in the ocular vessels of eyes with POAG (p < .01). The OA and medial posterior ciliary arteries RI was higher, and the OA EDV was lower in glaucomatous eyes with progressive than with stable visual field loss. The receiver operating characteristic curve showed the optimal cutoff RI to be 0.847. CONCLUSIONS: Ocular blood flow appears compromised in eyes with POAG, particularly in those with progressive visual field loss.

Low Dose Pediatric CT Head Protocol using Iterative Reconstruction Techniques: A Comparison with Standard Dose Protocol.

PURPOSE: Pediatric computed tomography (CT) head examination has also increased in recent years with the advancement in CT technology; however, children exposed to radiation at the youngest age are more vulnerable to the risks of radiation. The aim of the study is to evaluate radiation dose and image quality of low dose pediatric CT head protocol compared to standard dose pediatric CT head protocol. METHODS: This was a prospective study. Group 1 included 73 patients aged < 1 year and 70 patients in the 1-5 years age group and had undergone CT head examination using the standard dose protocol. Group 2 included 31 patients aged < 1 year and 40 patients in the 1-5 years age group and had undergone CT head examination using the low dose protocol. The radiation dose was measured and image quality was assessed quantitatively and qualitatively. RESULTS: There was a significant difference in radiation dose between the standard and low dose protocols (p > 0.05) with lower radiation dose for low dose group. The qualitative analysis did not show a significant difference between the standard and low dose protocols. The gray-white matter differentiation (GWMD), attenuation, contrast to noise ratio (CNR) and figure of merit (FOM) were higher in the low dose protocol compared to the standard dose with a significant difference (p > 0.05). CONCLUSION: The study concludes that a low dose protocol at 80 kV tube voltage/150 mAs tube current exposure time product/iterative reconstruction-iDose4 (level 3) for < 1 year age group and 100 kV/200m As/iDose4 (level 3) for 1-5 years age group provides ultra-low effective dose with diagnostically acceptable image quality for pediatric CT head examination compared with standard dose protocol.

Evaluation of positioning accuracy, radiation dose and image quality: artificial intelligence based automatic versus manual positioning for CT KUB.

Background: Recent innovations are making radiology more advanced for patient and patient services. Under the immense burden of radiology practice, Artificial Intelligence (AI) assists in obtaining Computed Tomography (CT) images with less scan time, proper patient placement, low radiation dose (RD), and improved image quality (IQ). Hence, the aim of this study was to evaluate and compare the positioning accuracy, RD, and IQ of AI-based automatic and manual positioning techniques for CT kidney ureters and bladder (CT KUB). Methods: This prospective study included 143 patients in each group who were referred for computed tomography (CT) KUB examination. Group 1 patients underwent manual positioning (MP), and group 2 patients underwent AI-based automatic positioning (AP) for CT KUB examination. The scanning protocol was kept constant for both the groups. The off-center distance, RD, and quantitative and qualitative IQ of each group were evaluated and compared. Results: The AP group (9.66±6.361 mm) had significantly less patient off-center distance than the MP group (15.12±9.55 mm). There was a significant reduction in RD in the AP group compared with that in the MP group. The quantitative image noise (IN) was lower, with a higher signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in the AP group than in the MP group (p<0.05). Qualitative IQ parameters such as IN, sharpness, and overall IQ also showed significant differences (p< 0.05), with higher scores in the AP group than in the MP group. Conclusions: The AI-based AP showed higher positioning accuracy with less off-center distance (44%), which resulted in 12% reduction in RD and improved IQ for CT KUB imaging compared with MP.

Comparison of image quality between Deep learning image reconstruction and Iterative reconstruction technique for CT Brain- a pilot study.

Background: Non-contrast Computed Tomography (NCCT) plays a pivotal role in assessing central nervous system disorders and is a crucial diagnostic method. Iterative reconstruction (IR) methods have enhanced image quality (IQ) but may result in a blotchy appearance and decreased resolution for subtle contrasts. The deep-learning image reconstruction (DLIR) algorithm, which integrates a convolutional neural network (CNN) into the reconstruction process, generates high-quality images with minimal noise. Hence, the objective of this study was to assess the IQ of the Precise Image (DLIR) and the IR technique (iDose 4) for the NCCT brain. Methods: This is a prospective study. Thirty patients who underwent NCCT brain were included. The images were reconstructed using DLIR-standard and iDose 4. Qualitative IQ analysis parameters, such as overall image quality (OQ), subjective image noise (SIN), and artifacts, were measured. Quantitative IQ analysis parameters such as Computed Tomography (CT) attenuation (HU), image noise (IN), posterior fossa index (PFI), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) in the basal ganglia (BG) and centrum-semiovale (CSO) were measured. Paired t-tests were performed for qualitative and quantitative IQ analyses between the iDose 4 and DLIR-standard. Kappa statistics were used to assess inter-observer agreement for qualitative analysis. Results: Quantitative IQ analysis showed significant differences (p<0.05) in IN, SNR, and CNR between the iDose 4 and DLIR-standard at the BG and CSO levels. IN was reduced (41.8-47.6%), SNR (65-82%), and CNR (68-78.8%) were increased with DLIR-standard. PFI was reduced (27.08%) the DLIR-standard. Qualitative IQ analysis showed significant differences (p<0.05) in OQ, SIN, and artifacts between the DLIR standard and iDose 4. The DLIR standard showed higher qualitative IQ scores than the iDose 4. Conclusion: DLIR standard yielded superior quantitative and qualitative IQ compared to the IR technique (iDose4). The DLIR-standard significantly reduced the IN and artifacts compared to iDose 4 in the NCCT brain.

Influence of deep learning image reconstruction algorithm for reducing radiation dose and image noise compared to iterative reconstruction and filtered back projection for head and chest computed tomography examinations: a systematic review.

Background: The most recent advances in Computed Tomography (CT) image reconstruction technology are Deep learning image reconstruction (DLIR) algorithms. Due to drawbacks in Iterative reconstruction (IR) techniques such as negative image texture and nonlinear spatial resolutions, DLIRs are gradually replacing them. However, the potential use of DLIR in Head and Chest CT has to be examined further. Hence, the purpose of the study is to review the influence of DLIR on Radiation dose (RD), Image noise (IN), and outcomes of the studies compared with IR and FBP in Head and Chest CT examinations. Methods: We performed a detailed search in PubMed, Scopus, Web of Science, Cochrane Library, and Embase to find the articles reported using DLIR for Head and Chest CT examinations between 2017 to 2023. Data were retrieved from the short-listed studies using Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Results: Out of 196 articles searched, 15 articles were included. A total of 1292 sample size was included. 14 articles were rated as high and 1 article as moderate quality. All studies compared DLIR to IR techniques. 5 studies compared DLIR with IR and FBP. The review showed that DLIR improved IQ, and reduced RD and IN for CT Head and Chest examinations. Conclusions: DLIR algorithm have demonstrated a noted enhancement in IQ with reduced IN for CT Head and Chest examinations at lower dose compared with IR and FBP. DLIR showed potential for enhancing patient care by reducing radiation risks and increasing diagnostic accuracy.