response to pressure increases produced by the arteriole. In fact, the capillaries staining positive for DsRed had a larger diameter than capillaries devoid of DsRed (4.62 6 0.09 vs 3.72 6 0.05 mm; P ¼ 2.7 · 10 27 ), suggesting that pericytes are implicated in increasing or decreas- ing capillary resistance and diameter. Furthermore, pericytes have been shown to promote constriction of retinal capillaries through an increase in intracellular Ca 21 , secondary to a loss of ATP-activated ion pumping channels during episodes of ischemia. 3 Even during the reperfusion period after an in vivo middle cerebral artery occlusion, there remains a long- lasting reduction of cerebral blood flow. 5 To gain a better understanding of the role of pericyte health on vascular resistance, the authors exam- ined pericyte survival by using propidium iodide as a cell death marker after induced ischemia. Within 15 minutes of ischemia (oxygen-glucose deprivation with ATP synthesis inhibition by iodoacetate and antimycin), gray matter capil- laries constricted near regions rich with pericytes. Forty minutes from the initial insult, most pericytes near the initial capillary constriction site were dead. These results suggest that pericytes initially constrict with ischemia and then eventually die, and this process results in an increase in capillary bed resistance. Revascularization leading to reperfusion re- mains the only effective treatment for patients with stroke. Unfortunately, ischemia may result in irreversible pericyte vasoconstriction in the capillary networks. Novel strategies to inhibit pericyte-induced microvascular vasoconstriction may ultimately allow improved perfusion of capillary-irrigated neurons and protect brain tissue after a stroke. Gregory M. Weiner, MD Andrew F. Ducruet, MD University of Pittsburgh Medical Center Pittsburgh, Pennsylvania REFERENCES 1. Hall CN, Attwell D. Assessing the physiological concentration and targets of nitric oxide in brain tissue. J Neurosci. 2012;32:8940-8951. 2. Puro DG. Physiology and pathobiology of the pericyte-containing retinal microvasculature: new developments. Microcirculation. 2007;14(1):1-10. 3. Peppiatt CM, Howard C, Mobbs P, Attwell D. Bidirectional control of CNS capillary diameter by pericytes. Nature. 2006;443(7112):700-704. 4. Hall CN, Reynell C, Gesslein B, et al. Capillary pericytes regulate cerebral blood flow in health and disease. Nature. 2014;508(7494):55-60. 5. Yernisci M, Gursoy-Ozdemir Y, Vural A, et al. Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nat Med. 2009;15:1031-1037. A Telomerase Assay Detects Brain Tumor Cells in Blood R ecent advances in biotechnology have helped to identify blood-based biomark- ers for a variety of cancers, including lung, breast, colorectal, and prostate. 1 The detection of tumor cells circulating in the peripheral blood- stream may be a useful strategy to monitor disease status, to gauge prognosis, and to guide treatment decisions for patients with primary brain cancers. 2 Currently available assays for identifying circulating tumor cells (CTCs) detect the epithelial cell surface markers common to many carcinomas of epithelial origin. 3 However, primary brain tumors are of glial origin and lack these cell surface markers, necessitating a different identification strategy. In a recent article published in Cancer Research, MacArthur et al 4 developed and studied a periph- eral blood assay that identifies circulating glioma cells using a novel adenoviral probe for tumor cell detection. They began by using immunofluores- cence staining to show that glioma cells over- express the protein telomerase, which enables cell renewal by maintaining the telomeres found at the ends of chromosomes. Conversely, they showed that telomerase is not overexpressed by normal glial cells. Next, they used an adenoviral probe 5 to introduce a fluorescent marker, green fluorescent protein, into the telomerase expression sequence of peripheral blood cells. This enabled them to identify the cells that overexpressed telomerase by measuring their elevated fluorescence. Using this technology, they determined the quantity of fluorescent cells in the peripheral blood of healthy volunteers. They also measured the quantity of fluorescent cells in the peripheral blood of patients with gliomas at a variety of pretreatment and posttreatment time points. They found that pretreatment glioma patients had elevated CTCs compared with healthy volunteers. Posttreatment glioma patients had reduced CTCs compared with pretreatment patients. In addition, serial, longitudinal CTC measurements in glioma patients correlated with disease progression. In current practice, radiographic monitoring of posttreatment gliomas is limited because imaging alone cannot definitively differentiate between true progressive disease, pseudoprog- ression, and radionecrosis. 6 The authors showed that in a pilot group of patients, longitudinal CTC measurements helped to clarify ambigu- ous imaging results. For example, rising CTCs in the setting of worsening radiographic findings correctly suggested progressive disease instead of pseudoprogression. Conversely, persistently low CTCs in the setting of worsening radiographic findings correctly suggested pseudoprogression. Despite the need for further clinical studies demonstrating the accuracy, reproducibility, and linearity of this novel assay, this research convincingly extends a safe and noninvasive cancer monitoring strategy to patients with primary brain tumors. The authors should be congratulated for their significant contribution. Benjamin M. Zussman, MD Phillip V. Parry, MD Johnathan A. Engh, MD University of Pittsburgh Medical Center Pittsburgh, Pennsylvania REFERENCES 1. Brenner DE, Normolle DP. Biomarkers for cancer risk, early detection, and prognosis: the validation conundrum. Cancer Epidemiol Biomarkers Prev. 2007; 16(10):1918-1920. 2. Paterlini-brechot P, Benali NL. Circulating tumor cells (CTC) detection: clinical impact and future directions. Cancer Lett. 2007;253(2):180-204. 3. Allard WJ, Matera J, Miller MC, et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004;10 (20):6897-6904. 4. Macarthur KM, Kao GD, Chandrasekaran S, et al. Detection of brain tumor cells in the peripheral blood by a telomerase promoter-based assay. Cancer Res. 2014;74(8):2152-2159. 5. Kojima T, Hashimoto Y, Watanabe Y, et al. A simple biological imaging system for detecting viable human circulating tumor cells. J Clin Invest. 2009;119(10): 3172-3181. 6. Hygino da cruz LC, Rodriguez I, Domingues RC, Gasparetto EL, Sorensen AG. Pseudoprogression and pseudoresponse: imaging challenges in the assessment of posttreatment glioma. AJNR Am J Neuroradiol. 2011;32(11):1978-1985. In Vivo Chemical Exchange Saturation Transfer Imaging Allows Early Detection of a Therapeutic Response in Glioblastoma I t can be a guessing game. Has the patient’s glioblastoma (GBM) responded to treat- ment, or has it progressed? Is what is seen on magnetic resonance imaging (MRI) pseudoprog- ression? Should the current therapy be aborted as a result, or should it be continued? 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