Reduction of intratumoral brain perfusion by noninvasive transcranial electrical stimulation

Abstract

Malignant brain neoplasms have a poor prognosis despite aggressive treatments. Animal models and evidence from human bodily tumors reveal that sustained reduction in tumor perfusion via electrical stimulation promotes tumor necrosis, therefore possibly representing a therapeutic option for patients with brain tumors. Here, we demonstrate that transcranial electrical stimulation (tES) allows to safely and noninvasively reduce intratumoral perfusion in humans. Selected patients with glioblastoma or metastasis underwent tES, while perfusion was assessed using magnetic resonance imaging. Multichannel tES was applied according to personalized biophysical modeling, to maximize the induced electrical field over the solid tumor mass. All patients completed the study and tolerated the procedure without adverse effects, with tES selectively reducing the perfusion of the solid tumor. Results potentially open the door to noninvasive therapeutic interventions in brain tumors based on stand-alone tES or its combination with other available therapies.

Network Mapping of Connectivity Alterations in Disorder of Consciousness: Towards Targeted Neuromodulation

“…This approach is applicable to all tES modalities (e.g. tACS, tDCS, tRNS) and had already been implemented successfully in healthy subjects [38][39][40] and patients [41][42][43].…”

Newly discovered neuron-to-glioma communication: new noninvasive therapeutic opportunities on the horizon?

“… 27 Image-guided, personalized tDCS targeting the solid tumor mass has been recently demonstrated able to transiently modify tumor perfusion in patients with glioblastoma and lung metastasis by our group, both pre- and postsurgery. 7 Based on similar evidence on bodily tumors (eg, spinal tumor, breast, and liver cancers 28 , 29 ) in which progressive perfusion reduction and necrosis have been observed after repetitive sessions of direct current stimulation delivered via electrodes directly inserted into the tumor, tDCS in gliomas may lead to long-lasting reduction of tumor perfusion and be leveraged to reduce tumor metabolism as well as growth. 28 , 29 tDCS has also been shown to transiently increase permeability of the blood–brain barrier (BBB) to small and large molecules (up to 70 kDa) in rats and endothelial monolayers, using stimulation intensities similar to those applied in humans (1 mA).…”

“…To date, no clinical trials have been conducted on brain tumor patients via TMS or tDCS, probably due to the lack of knowledge about noninvasive brain stimulation in the field of clinical neuro-oncology. Indeed, neuromodulation techniques have been developed and tested mainly by neurologists and psychiatrists given the possibility of interacting with neuronal activity and potentially restoring physiological function, 5 , 6 with extra-neuronal applications only now emerging (ie, brain perfusion modulation 7 ). Moreover, as for the application of neuromodulation to inhibit neuronal activity induced glioma growth, new insight on tumor electrical property supporting a new context for NiBS application has been shared very recently, and still need to be fully received by the clinical neuro-oncological community.…”

Personalised, image-guided, noninvasive brain stimulation in gliomas: Rationale, challenges and opportunities

“…A recent pilot study by our group tested this possibility in patients with GBM ( n = 6) and lung metastasis in the brain ( n = 2) [17] . Multifocal tDCS was delivered for 20 min with an MRI-compatible device while the patient was inside the MRI scanner allowing contemporaneous assessment of perfusion variation via a CBF-sensitive sequence (ASL) in a single experimental session.…”

“…On the other hand, NiBS could also affect tumour growth via non-neuronal effects. Indeed, NiBS has recently been found to modify cerebral and intratumoural perfusion [17] , the permeability of the blood brain barrier (BBB) [18] , and to interact with microglia [19] , suggesting additional interventional -still unexplored- noninvasive stimulation strategies for patients with brain tumours.…”