Beyond Visual Assessment of Basal Ganglia Uptake: Can Automated Method and Pineal Body Uptake Assessment Improve Identification of Nigrostriatal Dysfunction on 18F-DOPA PET/CT?

The interpretation of 18F-DOPA PET/CT performed for assessing nigrostriatal dysfunction (NSD) is usually based on visual assessment of the uptake in the basal ganglia (VA-BG). In the present study, we evaluate the diagnostic performance of an automated method that assesses BG uptake (AM-BG) and of methods that assess pineal body uptake, and examine whether these methods can enhance the diagnostic performance of VA-BG alone. We retrospectively included 112 scans performed in patients with clinically suspected NSD who also had a subsequent final clinical diagnosis provided by a movement disorder specialist (69 NSD and 43 non-NSD patients). All scans were categorized as positive or negative based on (1) VA-BG, (2) AM-BG, and (3) qualitative and semiquantitative assessment of pineal body uptake. VA-BG, AM-BG, assessment of pineal body 18F-DOPA uptake by VA (uptake > background), by SUVmax (≥0.72), and by pineal to occipital ratio (POR ≥ 1.57) could all significantly differentiate NSD from non-NSD patients (Pv < 0.01 for all five methods). Of these methods, VA-BG provided the highest sensitivity (88.4%) and accuracy (90.2%). Combining VA-BG with AM-BG did not improve diagnostic accuracy. An interpretation algorithm that combines VA-BG with pineal body uptake assessment by POR calculation increased sensitivity to 98.5%, at the expense of decreased specificity. In conclusion, an automated method that assesses 18F-DOPA uptake in the BG and assessment of pineal body 18F-DOPA uptake can significantly separate NSD from non-NSD patients, with apparent inferior diagnostic performance when applied alone compared with VA-BG. When VA-BG categorizes a scan as negative or equivocal, assessment of the 18F-DOPA uptake in the pineal body has the potential to minimize the rate of false negative reports. Further research is essential to validate this approach and to study the pathophysiologic relationship between 18F-DOPA uptake in the pineal body and nigrostriatal dysfunction.

Fluorescent Molecules That Help Reveal Previously Unidentified Neural Connections in Adult, Neonatal and Peripubertal Mammals.

One hundred and twenty-five years ago there was a lively discussion between Hungarian and Spanish neuroscientists on the nature of neural connections. The question was whether the neurofibrils run from one neuron to the next and connect neurons as a continuous network or the fibrils form an internal skeleton in the neurons and do not leave the cell; however, there is close contact between the neurons. About 50 years later, the invention of the electron microscope solved the problem. Close contacts between individual neurons were identified and named as synapses. In the following years, the need arose to explore distant connections between neuronal structures. Tracing techniques entered neuroscience. There are three major groups of tracers: (A) non-transsynaptic tracers used to find direct connections between two neuronal structures; (B) tracers passing gap junctions; (C) transsynaptic tracers passing synapses that are suitable to explore multineuronal circuits. According to the direction of the transport mechanism, the tracer may be ante- or retrograde. In this review, we focus on the ever-increasing number of fluorescent tracers that we have also used in our studies. The advantage of the use of these molecules is that the fluorescence of the tracer can be seen in histological sections without any other processes. Genes encoding fluorescent molecules can be inserted in various neuropeptide or neurotransmitter expressing transcriptomes. This makes it possible to study the anatomy, development or functional relations of these neuronal networks in transgenic animals.

Plasma miRNA expression profile in pediatric pineal pure germinomas.

Background: Pure germinomas account for 40% of pineal tumors and are characterized by the lack of appreciable tumor markers, thus requiring a tumor biopsy for diagnosis. MicroRNAs (miRNA) have emerged as potential non-invasive biomarkers for germ cell tumors and may facilitate the non-invasive diagnosis of pure pineal germinomas. Material and methods: A retrospective chart review was performed on all patients treated at the Children's Cancer Hospital Egypt diagnosed with a pineal region tumor between June 2013 and March 2021 for whom a research blood sample was available. Plasma samples were profiled for miRNA expression, and DESeq2 was used to compare between pure germinoma and other tumor types. Differentially expressed miRNAs were identified. The area under the curve of the receive;r operating characteristic curve was constructed to evaluate diagnostic performance. Results: Samples from 39 pediatric patients were available consisting of 12 pure germinomas and 27 pineal region tumors of other pathologies, including pineal origin tumors [n = 17; pineoblastoma (n = 13) and pineal parenchymal tumors of intermediate differentiation (n = 4)] and others [n = 10; low-grade glioma (n = 6) and atypical teratoid rhabdoid tumor (n = 4)]. Using an adjusted p-value <0.05, three miRNAs showed differential expression (miR-143-3p, miR-320c, miR-320d; adjusted p = 0.0058, p = 0.0478, and p = 0.0366, respectively) and good discriminatory power between the two groups (AUC 90.7%, p < 0.001) with a sensitivity of 25% and a specificity of 100%. Conclusion: Our results suggest that a three-plasma miRNA signature has the potential to non-invasively identify pineal body pure germinomas which may allow selected patients to avoid the potential surgical complications.

So-called bifocal tumors with diabetes insipidus and negative tumor markers: are they all germinoma?

BACKGROUND: The Delphi consensus statements on the management of germ cell tumors (GCTs) failed to reach agreements on the statement that the cases with (i) pineal and neurohypophyseal bifocal lesion, (ii) with diabetes insipidus, and (iii) with negative tumor markers can be diagnosed as germinoma without histological verification. To answer this, multicenter retrospective analysis was performed. METHODS: A questionnaire on clinical findings, histological diagnosis, and details of surgical procedures was sent to 86 neurosurgical and 35 pediatrics departments in Japan. RESULTS: Fifty-one institutes reported 132 cases that fulfilled the 3 criteria. Tissue sampling was performed in 91 cases from pineal (n = 44), neurohypophyseal (n = 32), both (n = 6), and distant (n = 9) lesions. Histological diagnosis was established in 89 cases: pure germinoma or germinoma with syncytiotrophoblastic giant cells in 82 (92.1%) cases, germinoma and mature teratoma in 2 cases, and granulomatous inflammation in 2 cases. Histological diagnosis was not established in 2 cases. Although no tumors other than GCTs were identified, 3 (3.4%) patients had non-germinomatous GCTs (NGGCTs). None of the patients developed permanent complications after endoscopic or stereotactic biopsy. Thirty-nine patients underwent simultaneous procedure for acute hydrocephalus without permanent complications, and hydrocephalus was controlled in 94.9% of them. CONCLUSION: All patients who fulfilled the 3 criteria had GCTs or granulomatous inflammation, but not other types of tumors. However, no fewer than 3.4% of the patients had NGGCTs. Considering the safety and the effects of simultaneous procedures for acute hydrocephalus, biopsy was recommended in such patients.

Topographical anatomy of the tentorium cerebelli and venous confluences in human midterm fetuses.

Early development of veins and sinuses at and around the posterior cranial fossa seemed not to be shown by photographs except for our recent study (Ann Anat, 2020). Examination of histological sections of 38 fetuses at 10-16 weeks gestational age (GA) demonstrated that: (1) the superior petrosal sinus passed posterosuperiorly through the tentorium cerebelli and, distant and lateral to both the cerebellum and internal ear, drained into the transverse sinus; (2) the superior sagittal sinus was underdeveloped, and the inferior sagittal sinus was not yet evident; (3) the straight sinus (STS) originated from a joining of the bilateral pial veins from the lateral ventricular choroid plexus, passed through the inferoposterior part of the falx cerebri, reached the initial confluens sinuum, and then divided into the bilateral transverse sinuses. The STS origin was immediately behind the pineal body, and near the inferoposterior end of the third ventricle. The falx had a thick attachment to the tentorium below the entire course of the STS and was behind other parts of the brain. Therefore, the development and growth of the posterior dural system seemed to be independent from brain growth, and occurred well before the cerebellum grew to fill the posterior cranial fossa. A basic configuration of intracranial veins and sinuses, including embryonic transient veins (such as the vena capitis prima) seemed to be established by venous return from the choroid plexus and cranial wall, without greatly increasing the abundance of neuronal or glial cells in the brain.

Anatomical study of the pineal gland in capybara (Hydrochoerus hydrochoeris) / Pesquisa anatômica da glândula pineal em capivaras (Hydrochoerus hydrochoeris)

The pineal gland was studied macro-and microscopically in 19 adult and young capybaras (Hydrochoerus hydrochoeris) 13 females and 6 males. Pineal gland was present in all specimens between the cerebrum and the cerebellum and was formed by a base with two peduncles, a stem and an apex. The gland was in the roof of the III ventricle, next to the rostral coliculi, eitherwhish or brownish.The apex contained a cavity. Pineal gland was 2.2 cm long, and dimensions of the base, stem and apex were 1.3 mm, 1.2 mm and 2.0 mm respectively. The connective tissue capsule at least in part, contained blood vessels. Pineal parenchyma exhibited pinealocytes, with nuclear and interstitial cells.

A glândula pineal foi estudada macro e microscopicamente em 19 capivaras (Hydrochoerus hydrochoeris) jovens e adultas, fêmeas e machos. A pineal, presente em todos os espécimes, estava localizada entre o cérebro e o cerebelo, e era formada por uma base com dois pedúnculos, uma haste e um ápice. A glândula localizava-se no teto do III ventrículo, próximo ao colículorostral, mostrando-se esbranquiçada ou acastanhada. O ápice continha uma cavidade. O comprimento médio da glândula na base foi de 1,3 mm; 1,2 mm; 2,0 mm na sua haste e ápice respectivamente. Revestida por uma cápsula de tecido conjuntivo contendo, pelo menos em parte do seu contorno, vasos sangüíneos, o parênquima pineal mostrou pinealócitos com grânulosnucleares e células intersticiais.