IN VIVO MAPPING BRAIN MICROCIRCULATION BY LASER SPECKLE CONTRAST IMAGING:A MAGNETIC RESONANCE PERSPECTIVE OF THEORETICAL FRAMEWORK

The fundamental limitations of most vascular-based functional neuroimaging techniques are placed by the fact how fine the brain regulates the blood supply system.In vivo mapping of the cerebral microcirculation with high resolution and sensitivity hence becomes unprecedentedly compelling.This paper reviews the theoretical background of the laser speckle contrast imaging(LSCI)technique and attempts to present a complete framework stemming from a simple biophysical model.Through the sensitivity analysis,more insights into the tool optimization are attained for in vivo applications.Open questions of the technical aspects are discussed within this unified framework.Finally,it concludes with a brief perspective of future research in a way analogous to the magnetic resonance imaging(MRI)technique.Such exploration could catalyze their development and initiate a technological fusion for precise assessment of blood flow across various spatial scales.

IN VIVO NEAR-INFRAREDFLUORESCENCEIMAGING OF HUMANCOLONADENOCARCINOMABY SPECIFIC IMMUNOTARGETINGOFA TUMOR-ASSOCIATEDMUCIN

Background and Aims: Accurate endoscopic detection of premalignant lesions and earlycancers in the colon is essential for cure, since prognosis is closely related to lesion size andstage. Although it has great clinical potential, autofluorescence endoscopy has limited tumorto-normal tissue image contrast for detecting small preneoplastic lesions. We have developed amolecularly specific, near-infrared fluorescent monoclonal antibody (CC49) bioconjugate whichtargets tumor-associated glycoprotein 72 (TAG72), as a contrast agent to improve fluorescencebased endoscopy of colon cancer. Methods: The fluorescent anti-TAG72 conjugate was evaluated in vitro and in vivo in athymic nude mice bearing human colon adenocarcinoma (LS174T)subcutaneous tumors. Autofluorescence, a fluorescent but irrelevant antibody and the free fluorescent dye served as controls. Fluorescent agents were injected intravenously, and in vivowhole body fluorescence imaging was performed at various time points to determine pharmacokinetics, followed by ex vivo tissue analysis by confocal fluorescence microscopy and histology Results: Fluorescence microscopy and histology confirmed specific LS174T cell membrane targeting of labeled CC49 in vitro and ex vivo. In vivo fluorescence imaging demonstrated significant tumor-to-normal tissue contrast enhancement with labeled-CC49 at three hours postinjection, with maximum contrast after 48 h. Accumulation of tumor fluorescence demonstratedthat modification of CC49 antibodies did not alter their specific tumor-localizing properties, andwas antibody-dependent since controls did not produce detectable tumor fluorescence. Conclusions: These results show proof-of-principle that our near-infrared fluorescent-antibody probetargeting a tumor-associated mucin detects colonic tumors at the molecular level in real time,and offer a basis for future improvement of image contrast during clinical fluorescence endoscopy.

Cough Modulation by Upper Airway Stimuli in Cat—Potential Clinical Application?

The modulation of mechanically induced tracheobronchial cough was tested by applying various stimuli and the elicitation of other airway protective behaviors in pentobarbital anesthetized cats. Capsaicin and histamine were injected in the nose, and mechanical nylon fiber and/or air puff stimulation was applied to the nose and nasopharynx. Reflex responses of cough, sneeze, aspiration reflex and expiration reflex were induced mechanically. Swallow was initiated by the injection of water into oropharynx. Subthreshold mechanical stimulation of nasopharyngeal and nasal mucosa, as well as water stimulation in the oropharynx and larynx, with no motor response, had no effect on rhythmic coughing. Cough responsiveness and excitability increased with capsaicin and air puff stimuli delivered to the nose. Vice versa, the number of cough responses was reduced and cough latency increased when aspiration reflexes (>1) occurred before the cough stimulus or within inter-cough intervals (passive E2 cough phase). The occurrence of swallows increased the cough latency as well. Cough inspiratory and/or expiratory motor drive was enhanced by the occurrence of expiration reflexes, swallows, and sneezes and also by aspiration reflex within the inspiratory phase of cough and by nasal air puff stimuli. Complex central interactions, ordering and sequencing of motor acts from the airways may result in the disruption of cough rhythmic sequence but also in the enhancement of cough. Our data confirm that number of peripheral stimuli and respiratory motor responses significantly alters cough performance. We propose developing and testing stimulation paradigms that modify coughing and could be employed in correcting of inappropriate or excessive coughing.