Tesi etd-11132020-171012
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Tipo di tesi
Corso Ordinario Ciclo Unico 6 Anni
Autore
CARATOZZOLO, DANIELE
URN
etd-11132020-171012
Titolo
Mapping human central chemoreceptors through Brainstem resting state functional Magnetic Resonance Imaging
Struttura
Cl. Sc. Sperimentali - Medicina
Corso di studi
SCIENZE MEDICHE - SCIENZE MEDICHE
Commissione
Tutor Prof. PASSINO, CLAUDIO
Presidente Prof. EMDIN, MICHELE
Membro Prof. COCEANI, FLAVIO
Membro Dott.ssa CASIERI, VALENTINA
Membro Prof. LIONETTI, VINCENZO
Membro Prof. RECCHIA, FABIO ANASTASIO
Membro Dott.ssa ANGELONI, DEBORA
Membro Dott. MEOLA, MARIO
Membro Dott.ssa PETRUCCI, ILARIA
Membro Dott. GIANNONI, ALBERTO
Presidente Prof. EMDIN, MICHELE
Membro Prof. COCEANI, FLAVIO
Membro Dott.ssa CASIERI, VALENTINA
Membro Prof. LIONETTI, VINCENZO
Membro Prof. RECCHIA, FABIO ANASTASIO
Membro Dott.ssa ANGELONI, DEBORA
Membro Dott. MEOLA, MARIO
Membro Dott.ssa PETRUCCI, ILARIA
Membro Dott. GIANNONI, ALBERTO
Parole chiave
- Nessuna parola chiave trovata
Data inizio appello
15/12/2020;
Disponibilità
completa
Riassunto analitico
Background Whether and where does the human brainstem (BS) harbor chemoreceptors involved into breathing control, is a question challenged on two fronts. Ventilatory responsiveness to microinjection of acetazolamide, microdiffusion of CO2 or microdialysis of serotoninergic drugs into animal BS nuclei such as Retrotrapezoid Nucleus (RTN), Pre-Boetzinger Complex (preBotC) and Locus Coeruleus (LC), suggests a first front to dig in. On the other hand, anatomical homologous of these BS nuclei derived from newborns died of Sudden Infant Death Syndrome (SIDS), show significant neuronal loss when compared to non-SIDS specimens. Similar histopathologic evidences have been found in patients with central apneas and Multiple Systems Athropy (MSA).
Here we suggest brainstem resting state functional magnetic resonance imaging (BS-rsfMRI) as a new method to finally investigate in vivo human BS chemoceptors on another pathologic model: central apnea in patients suffering from heart failure (HF). Rationale for this purpose roots into the BREATH study, a randomized, double-blind, placebo-controlled crossover trial demonstrating the serotoninergic agonist buspirone as effective in lowering chemosensitivity and central apneas in patients with HF.
Methods n=8 patients suffering from HF with reduced or mid-range ejection fraction underwent 24-h respiratory recording to assess diurnal central aponea/hypopnoea index (dAHI) and chemoreflex assay. n=4 patients with hypercapnic ventilatory response slope below the median joined the high-normal chemosensitivity group (h-nCS), while n=4 patients were part of abnormal chemosensitivity group (aCS). Contrast-enhanced ultrasound provided measures to calculate lung to carotid circulation time (tL->C). Then BS-rsfMRI acquisition were performed with a 3.5 T MRI scanner and at same time capnogram has been acquired. BOLD signals underwent Independent Component Analysis (ICA) to compute cross-correlation, within the 2*tL->C range of time, between signal components and capnogram envelope (end tidal CO2, approximation of alveolar CO2). Areas, where signals with significant correlations arose, were then highlighted on an anatomical map of putative human central chemoreceptors.
Results Brainstem activity has been found in both h-nCS and aCS groups within Medullary Raphe Region. Furthermore, aCS patients show BOLD components coherent with a phase to capnogram envelope (end tidal CO2), in areas where putative Retrotrapezoid nucleus and pre-Botzinger Complex have been located in previous autoptic studies.
Conclusions Resting state functional magnetic resonance imaging is a feasible and promising technique to locate chemoreceptors within the human brainstem.
Here we suggest brainstem resting state functional magnetic resonance imaging (BS-rsfMRI) as a new method to finally investigate in vivo human BS chemoceptors on another pathologic model: central apnea in patients suffering from heart failure (HF). Rationale for this purpose roots into the BREATH study, a randomized, double-blind, placebo-controlled crossover trial demonstrating the serotoninergic agonist buspirone as effective in lowering chemosensitivity and central apneas in patients with HF.
Methods n=8 patients suffering from HF with reduced or mid-range ejection fraction underwent 24-h respiratory recording to assess diurnal central aponea/hypopnoea index (dAHI) and chemoreflex assay. n=4 patients with hypercapnic ventilatory response slope below the median joined the high-normal chemosensitivity group (h-nCS), while n=4 patients were part of abnormal chemosensitivity group (aCS). Contrast-enhanced ultrasound provided measures to calculate lung to carotid circulation time (tL->C). Then BS-rsfMRI acquisition were performed with a 3.5 T MRI scanner and at same time capnogram has been acquired. BOLD signals underwent Independent Component Analysis (ICA) to compute cross-correlation, within the 2*tL->C range of time, between signal components and capnogram envelope (end tidal CO2, approximation of alveolar CO2). Areas, where signals with significant correlations arose, were then highlighted on an anatomical map of putative human central chemoreceptors.
Results Brainstem activity has been found in both h-nCS and aCS groups within Medullary Raphe Region. Furthermore, aCS patients show BOLD components coherent with a phase to capnogram envelope (end tidal CO2), in areas where putative Retrotrapezoid nucleus and pre-Botzinger Complex have been located in previous autoptic studies.
Conclusions Resting state functional magnetic resonance imaging is a feasible and promising technique to locate chemoreceptors within the human brainstem.
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