Real-time influence of intracellular acidification and Na+ /H+ exchanger inhibition on in-cell pyruvate metabolism in the perfused mouse heart: A 31 P-NMR and hyperpolarized 13 C-NMR study.

Disruption of acid-base balance is linked to various diseases and conditions. In the heart, intracellular acidification is associated with heart failure, maladaptive cardiac hypertrophy, and myocardial ischemia. Previously, we have reported that the ratio of the in-cell lactate dehydrogenase (LDH) to pyruvate dehydrogenase (PDH) activities is correlated with cardiac pH. To further characterize the basis for this correlation, these in-cell activities were investigated under induced intracellular acidification without and with Na+ /H+ exchanger (NHE1) inhibition by zoniporide. Male mouse hearts (n = 30) were isolated and perfused retrogradely. Intracellular acidification was performed in two ways: (1) with the NH4 Cl prepulse methodology; and (2) by combining the NH4 Cl prepulse with zoniporide. 31 P NMR spectroscopy was used to determine the intracellular cardiac pH and to quantify the adenosine triphosphate and phosphocreatine content. Hyperpolarized [1-13 C]pyruvate was obtained using dissolution dynamic nuclear polarization. 13 C NMR spectroscopy was used to monitor hyperpolarized [1-13 C]pyruvate metabolism and determine enzyme activities in real time at a temporal resolution of a few seconds using the product-selective saturating excitation approach. The intracellular acidification induced by the NH4 Cl prepulse led to reduced LDH and PDH activities (-16% and -39%, respectively). This finding is in line with previous evidence of reduced myocardial contraction and therefore reduced metabolic activity upon intracellular acidification. Concomitantly, the LDH/PDH activity ratio increased with the reduction in pH, as previously reported. Combining the NH4 Cl prepulse with zoniporide led to a greater reduction in LDH activity (-29%) and to increased PDH activity (+40%). These changes resulted in a surprising decrease in the LDH/PDH ratio, as opposed to previous predictions. Zoniporide alone (without intracellular acidification) did not change these enzyme activities. A possible explanation for the enzymatic changes observed during the combination of the NH4 Cl prepulse and NHE1 inhibition may be related to mitochondrial NHE1 inhibition, which likely negates the mitochondrial matrix acidification. This effect, combined with the increased acidity in the cytosol, would result in an enhanced H+ gradient across the mitochondrial membrane and a temporarily higher pyruvate transport into the mitochondria, thereby increasing the PDH activity at the expense of the cytosolic LDH activity. These findings demonstrate the complexity of in-cell cardiac metabolism and its dependence on intracellular acidification. This study demonstrates the capabilities and limitations of hyperpolarized [1-13 C]pyruvate in the characterization of intracellular acidification as regards cardiac pathologies.

Accumulation of 3-aminopropylphosphonate in the ex vivo brain observed by phosphorus-31 nuclear magnetic resonance.

3-aminopropylphosphonate (3-APP) is known for its use as an exogenous indicator of extracellular volume and pH in phosphorus-31 nuclear magnetic resonance (31 P NMR) studies. We used 3-APP for estimating the extracellular volume in NMR studies of several ex vivo preparations including retrograde perfused mouse heart (n = 4), mouse liver slices (n = 2), xenograft breast cancer tumors (n = 7, MCF7), and rat brain slices (n = 4). In the former three preparations, the 3-APP signal was stable in lineshape and intensity for hours and the chemical shift of the signal in the presence of the biological sample was the same as in the perfusion medium without the biological sample. However, in studies of brain slices, the 3-APP signal appeared split into two, with an upfield component (0.7 ± 0.1 ppm to the left) increasing with time and showing a wider linewidth (66.7 ± 12.6 vs. 39.1 ± 7.6 Hz, the latter is of the perfusion medium signal). This finding suggests that 3-APP inadvertently accumulated in brain slices, most likely as a membrane bound form. This observation limits the use of 3-APP as an inert biochemical indicator in brain preparations and should be taken into account when using 3-APP in vivo.

Curbing action potential generation or ATP-synthase leads to a decrease in in-cell pyruvate dehydrogenase activity in rat cerebrum slices.

Direct and real-time monitoring of cerebral metabolism exploiting the drastic increase in sensitivity of hyperpolarized 13C-labeled metabolites holds the potential to report on neural activity via in-cell metabolic indicators. Here, we followed the metabolic consequences of curbing action potential generation and ATP-synthase in rat cerebrum slices, induced by tetrodotoxin and oligomycin, respectively. The results suggest that pyruvate dehydrogenase (PDH) activity in the cerebrum is 4.4-fold higher when neuronal firing is unperturbed. The PDH activity was 7.4-fold reduced in the presence of oligomycin, and served as a pharmacological control for testing the ability to determine changes to PDH activity in viable cerebrum slices. These findings may open a path towards utilization of PDH activity, observed by magnetic resonance of hyperpolarized 13C-labeled pyruvate, as a reporter of neural activity.

First multicenter experience using the Silk Vista flow diverter in 60 consecutive intracranial aneurysms: technical aspects.

BACKGROUND: The aim of this study was to assess the technical success and procedural safety of the new Silk Vista device (SV) by evaluating the intraprocedural and periprocedural complication rate after its use in several institutions worldwide. METHODS: The study involved a retrospective review of multicenter data regarding a consecutive series of patients with intracranial aneurysms, treated with the SV between September 2020 and January 2021. Clinical, intra/periprocedural and angiographic data, including approach, materials used, aneurysm size and location, device/s, technical details and initial angiographic aneurysm occlusion, were analyzed. RESULTS: 60 aneurysms were treated with SV in 57 procedures. 66 devices were used, 3 removed and 63 implanted. The devices opened instantaneously in 60 out of 66 (91%) cases and complete wall apposition was achieved in 58 out of 63 (92%) devices implanted. In 4 out of 66 (6%) devices a partial opening of the distal end occurred, and in 5 (8%) devices incomplete apposition was reported. There were 3 (5%) intraprocedural thromboembolic events managed successfully with no permanent neurological morbidity, and 4 (7%) postprocedural events. There was no mortality in this study. The initial occlusion rates in the 60 aneurysms were as follows: O'Kelly-Marotta (OKM) A in 34 (57%) cases, OKM B in 15 (25%) cases, OKM C in 6 (10%) cases, and OKM D in 5 (8%) cases. CONCLUSIONS: Our study demonstrated that the use of the new flow diverter Silk Vista for the treatment of intracranial aneurysms is feasible and technically safe.

The metabolic representation of ischemia in rat brain slices: A hyperpolarized 13 C magnetic resonance study.

The ischemic penumbra in stroke is not clearly defined by today's available imaging tools. This study aimed to develop a model system and noninvasive biomarkers of ischemic brain tissue for an examination that might potentially be performed in humans, very quickly, in the course of stroke triage. Perfused rat brain slices were used as a model system and 31 P spectroscopy verified that the slices were able to recover from an ischemic insult of about 3.5 min of perfusion arrest. This was indicated as a return to physiological pH and adenosine triphosphate levels. Instantaneous changes in lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) activities were monitored and quantified by the metabolic conversions of hyperpolarized [1-13 C]pyruvate to [1-13 C]lactate and [13 C]bicarbonate, respectively, using 13 C spectroscopy. In a control group (n = 8), hyperpolarized [1-13 C]pyruvate was administered during continuous perfusion of the slices. In the ischemia group (n = 5), the perfusion was arrested 30 s prior to administration of hyperpolarized [1-13 C]pyruvate and perfusion was not resumed throughout the measurement time (approximately 3.5 min). Following about 110 s of the ischemic insult, LDH activity increased by 80.4 ± 13.5% and PDH activity decreased by 47.8 ± 25.3%. In the control group, the mean LDH/PDH ratio was 16.6 ± 3.3, and in the ischemia group, the LDH/PDH ratio reached an average value of 38.7 ± 16.9. The results suggest that monitoring the activity of LDH and PDH, and their relative activities, using hyperpolarized [1-13 C]pyruvate, could serve as an imaging biomarker to characterize the changes in the ischemic penumbra.

Hyperpolarized product selective saturating-excitations for determination of changes in metabolic reaction rates in real-time.

Investigation of hyperpolarized substrate metabolism has been showing utility in real-time determination of in-cell and in vivo enzymatic activities. Intracellular reaction rates may vary during the course of a measurement, even on the very short time scales of visibility on hyperpolarized MR, due to many factors such as the availability of the substrate and co-factors in the intracellular space. Despite this potential variation, the kinetic analysis of hyperpolarized signals typically assumes that the same rate constant (and in many cases, the same rate) applies throughout the course of the reaction as observed via the build-up and decay of the hyperpolarized signals. We demonstrate here an acquisition approach that can null the need for such an assumption and enable the detection of instantaneous changes in the rate of the reaction during an ex vivo hyperpolarized investigation, (i.e. in the course of the decay of one hyperpolarized substrate dose administered to a viable tissue sample ex vivo). This approach utilizes hyperpolarized product selective saturating-excitation pulses. Similar pulses have been previously utilized in vivo for spectroscopic imaging. However, we show here favorable consequences to kinetic rate determinations in the preparations used. We implement this acquisition strategy for studies on perfused tissue slices and develop a theory that explains why this particular approach enables the determination of changes in enzymatic rates that are monitored via the chemical conversions of hyperpolarized substrates. Real-time changes in intracellular reaction rates are demonstrated in perfused brain, liver, and xenograft breast cancer tissue slices and provide another potential differentiation parameter for tissue characterization.

[13C6,D8]2-deoxyglucose phosphorylation by hexokinase shows selectivity for the ß-anomer.

A non-radioactive 2-deoxyglucose (2DG) analog has been developed here for hyperpolarized magnetic resonance investigations. The analog, [13C6,D8]2DG, showed 13% polarization in solution (27,000-fold signal enhancement at the C1 site), following a dissolution-DNP hyperpolarization process. The phosphorylation of this analog by yeast hexokinase (yHK) was monitored in real-time with a temporal resolution of 1 s. We show that yHK selectively utilizes the ß anomer of the 2DG analog, thus revealing a surprising anomeric specificity of this reaction. Such anomeric selectivity was not observed for the reaction of yHK or bacterial glucokinase with a hyperpolarized glucose analog. yHK is highly similar to the human HK-2, which is overexpressed in malignancy. Thus, the current finding may shed a new light on a fundamental enzyme activity which is utilized in the most widespread molecular imaging technology for cancer detection - positron-emission tomography with 18F-2DG.

In-cell determination of Lactate Dehydrogenase Activity in a Luminal Breast Cancer Model ⁻ ex vivo Investigation of Excised Xenograft Tumor Slices Using dDNP Hyperpolarized [1-13C]pyruvate.

[1-13C]pyruvate, the most widely used compound in dissolution-dynamic nuclear polarization (dDNP) magnetic resonance (MR), enables the visualization of lactate dehydrogenase (LDH) activity. This activity had been demonstrated in a wide variety of cancer models, ranging from cultured cells, to xenograft models, to human tumors in situ. Here we quantified the LDH activity in precision cut tumor slices (PCTS) of breast cancer xenografts. The Michigan Cancer Foundation-7 (MCF7) cell-line was chosen as a model for the luminal breast cancer type which is hormone responsive and is highly prevalent. The LDH activity, which was manifested as [1-13C]lactate production in the tumor slices, ranged between 3.8 and 6.1 nmole/nmole adenosine tri-phosphate (ATP) in 1 min (average 4.6 ± 1.0) on three different experimental set-ups consisting of arrested vs. continuous perfusion and non-selective and selective RF pulsation schemes and combinations thereof. This rate was converted to an expected LDH activity in a mass ranging between 3.3 and 5.2 µmole/g in 1 min, using the ATP level of these tumors. This indicated the likely utility of this approach in clinical dDNP of the human breast and may be useful as guidance for treatment response assessment in a large number of tumor types and therapies ex vivo.

Real-time ALT and LDH activities determined in viable precision-cut mouse liver slices using hyperpolarized [1-13 C]pyruvate-Implications for studies on biopsied liver tissues.

Precision-cut liver slices (PCLS) are widely used in liver research as they provide a liver model with all liver cell types in their natural architecture. The purpose of this study was to demonstrate the use of PCLS for hyperpolarized metabolic investigation in a mouse model, for potential future application in liver biopsy cores. Fresh normal liver was harvested from six mice. 500 µm PCLS were prepared and placed in a 10 mm NMR tube in an NMR spectrometer and perfused continuously. 31 P spectra were acquired to evaluate the presence of adenosine triphosphate (ATP) and validate viability in all samples. Hyperpolarized [1-13 C]pyruvate was flushed into the NMR tube in the spectrometer. Consecutive 13 C NMR spectra were acquired immediately after the injection using both non-selective (five injections, two livers) and selective RF excitation (six injections, three livers). The 31 P spectra showed the characteristic signals of ATP, confirming the viability of the PCLS for more than 2.5 h in the spectrometer. After each of the [1-13 C]pyruvate injections, both [1-13 C]lactate and [1-13 C]alanine signals were detected. Selective RF excitation aimed at both [1-13 C]lactate and [1-13 C]alanine enabled better visualization and quantification of the metabolic activity. Using this acquisition approach only the newly formed metabolites are observed upon excitation, and their intensities relative to those of hyperpolarized pyruvate enable quantification of metabolite production rates. This rate of lactate and alanine production appeared to be constant throughout the measurement time, with alanine production about 2.3 times higher than lactate. In summary, the viability of PCLS in an NMR spectrometer was demonstrated and hyperpolarized [1-13 C]pyruvate metabolism was recorded. This study opens up the possibility of evaluating alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities in human liver biopsies, while preserving the tissue architecture and viability. In healthy, well-perfused liver slices the ratio of ALT to LDH activity is about 2.3.

Stent and flow diverter assisted treatment of acutely ruptured brain aneurysms.

OBJECTIVE: We present our experience with stent techniques in the management of acutely ruptured aneurysms, focusing on aneurysm occlusion rates, intraprocedural complications, and late outcomes. METHODS: We retrospectively reviewed the clinical records of patients treated by stent techniques during the early acute phase of aneurysmal rupture, from June 2011 to June 2016. Patients who underwent stenting for the management of unruptured aneurysms, or in a delayed fashion for a ruptured lesion, were excluded. RESULTS: 47 patients met inclusion criteria, including 46 with subarachnoid hemorrhage (SAH). There were 27 men and 20 women, mean age 38 years (range 23-73). They harbored 71 aneurysms, including 56 treated in the acute phase. Aneurysmal dome and neck width averaged 4.7 mm (range 1.7-12.1) and 3.2 mm (range 1.5-7.1), respectively. Single stent techniques were used in 39 patients and dual stent techniques in 17. External ventricular drains (EVDs) were placed before embolization in 35 patients (92%) and after in 3. Intraprocedure thromboembolic complications due to a hyporesponse to antiplatlets in 4 patients (8.5%) were successfully managed with intra-arterial antiplatelet agents. In 45 surviving patients (96%), there was complete aneurysm occlusion at the 9-12 month follow-up in 26/29 aneurysms treated by stent-assisted coiling (90%), in 2/3 aneurysms treated by flow diverter-assisted coiling (66%), and in 19/22 aneurysms treated by flow diverter alone (86%); 42/45 patients (93%) presented with a modified Rankin Scale score of 0-2. CONCLUSION: Stenting techniques in ruptured aneurysms can be performed with good technical success; however, procedural thromboembolic complications related to the antiplatelet strategy merit investigation. EVD placement before stenting must be considered.

Biochemical phosphates observed using hyperpolarized 31P in physiological aqueous solutions.

The dissolution-dynamic nuclear polarization technology had previously enabled nuclear magnetic resonance detection of various nuclei in a hyperpolarized state. Here, we show the hyperpolarization of 31P nuclei in important biological phosphates (inorganic phosphate and phosphocreatine) in aqueous solutions. The hyperpolarized inorganic phosphate showed an enhancement factor >11,000 (at 5.8 T, 9.3% polarization) in D2O (T1 29.4 s). Deuteration and the solution composition and pH all affected the lifetime of the hyperpolarized state. This capability opens up avenues for real-time monitoring of phosphate metabolism, distribution, and pH sensing in the live body without ionizing radiation. Immediate changes in the microenvironment pH have been detected here in a cell-free system via the chemical shift of hyperpolarized inorganic phosphate. Because the 31P nucleus is 100% naturally abundant, future studies on hyperpolarized phosphates will not require expensive isotope labeling as is usually required for hyperpolarization of other substrates.Real-time monitoring of phosphate metabolism and distribution in the live body without ionizing radiation is highly desirable. Here, the authors show dissolution-dynamic nuclear polarization technology can enable nuclear magnetic resonance detection of hyperpolarized 31P of important biological phosphates in aqueous solutions.

Defective ATP breakdown activity related to an ENTPD1 gene mutation demonstrated using 31P NMR spectroscopy.

The ecto-nucleoside triphosphate diphosphohydrolase-1 (E-NTPDase-1, CD39) enzyme is responsible for the breakdown of extracellular ATP to ADP and then to AMP by a two-step process. Defective CD39 activity has been described in a variety of medical conditions including malignancy and rheumatic diseases and has been proved to be of major diagnostic and clinical importance. Here we show for the first time that a 31P NMR spectroscopy methodology enables the quantification of these two steps in a single blood sample. We have applied this assay to determine the E-NTPDase activity on human mononuclear cells taken from two siblings affected by a stop-codon mutation in the ENTPD1 gene, their obligatory heterozygous parents, and healthy volunteers. The affected subjects presented low ATP breakdown activity, mainly expressed as low AMP production.

Primary pleomorphic liposarcoma of the thoracic epidural space: case report.

BACKGROUND CONTEXT: Pleomorphic liposarcoma (PLS) is a rare malignant soft tissue tumor comprising 5%-15% of liposarcomas and characterized by high malignant potential. To our knowledge only three cases of this entity have been reported in the spine. PURPOSE: We describe the only reported case of a purely epidural PLS with no macroscopic bone involvement at diagnosis. STUDY DESIGN/SETTING: A case presenting clinical evidence that PLS may arise from the epidural fat is reported. METHODS: The clinical presentation, management, and outcome in a case of primary PLS of the thoracic spine, and a review of the literature, are presented. RESULTS: A 70-year-male presented with sudden onset lower extremity weakness, constipation, and back pain. Magnetic resonance imaging revealed an epidural lesion at T5 with noted mass effect compressing the spinal cord and extension to the T5-T6 foramen. Urgent decompressive laminectomy with gross total resection was performed. Histopathology revealed high-grade PLS. Adjunct radiotherapy was prescribed. The tumor recurred 3 months later. In spite of repeat surgery, additional radiation, and chemotherapy, the patient developed widespread metastases and succumbed to his disease 1 year after treatment began. CONCLUSIONS: Spinal PLS is a rare entity, but nonetheless may arise from epidural fat and should be considered in the differential diagnosis of primary spinal cord lesions.

Extracranial carotid artery stenting followed by intracranial stent-based thrombectomy for acute tandem occlusive disease.

OBJECTIVE: Acute tandem occlusions of the extracranial internal carotid artery (ICA) and a major intracranial artery respond poorly to intravenous tissue plasminogen activator (tPA) and present an endovascular challenge. We describe our experience with emergency stent-assisted ICA angioplasty and intracranial stent-based thrombectomy of tandem occlusions. METHODS: Procedures were performed from March 2010 to December 2013. National Institutes of Health Stroke Score (NIHSS) and Alberta Stroke Program Early CT Score (ASPECTS), occlusion sites, collateral supply, procedural details, and outcomes were retrospectively reviewed with IRB waiver of informed consent. RESULTS: 24 patients, mean age 66 years, mean admission NIHSS 20.4, and mean ASPECTS 9 were included. Occlusion sites were proximal ICA-middle cerebral artery (MCA) trunk in 17 patients, proximal ICA-ICA terminus in six, and ICA-MCA-anterior cerebral artery in one. Stent-assisted cervical ICA recanalization was achieved in all patients, with unprotected pre-angioplasty in 24/24, unprotected stenting in 16/24 (67%), and protected stenting in 8/24 (33%), followed by stent-thrombectomy in 25 intracranial occlusions. There was complete recanalization/complete perfusion in 19/24 (79%), complete recanalization/partial perfusion in 3/24 (13%), and partial recanalization/partial perfusion in 2/24 (8%) with no procedural morbidity/mortality. Mean time to therapy was 3.8 h (range 2-5.5) and mean time to recanalization was 51 min (range 38-69). At 3-month follow-up, among 17/22 surviving patients (77%), 13/17 (76%) were modified Rankin Scale (mRS) 0-2 and 3/17 (18%) were mRS 3. CONCLUSIONS: In acute tandem ICA-MCA/distal ICA occlusions, extracranial stenting followed by intracranial stent-based thrombectomy appears feasible, effective, and safe. Further evaluation of this treatment strategy is warranted.

Urgent off-label use of the pipeline flow diverter stent in selected ischemic cerebrovascular conditions: thrombotic segments and tortuous arteries.

OBJECTIVE: Flow diverter stents were originally designed for the endovascular management of certain types of cerebral aneurysms; however, these devices present characteristics that make them more suitable that regular carotid stents or neurostents for the management of selected ischemic cerebrovascular conditions. METHODS: Eight patients with steno-occlusive disease of the internal carotid (ICA) or vertebral (VA) arteries underwent endovascular reconstruction by means of flow diverter stent implant at our center. Five patients presented with ICA steno-occlusive lesions that involved tortuous segments not amenable to regular carotid stent placement and three patients presented with severe and complex proximal VA dissections. RESULTS: In all cases the procedures were considered technically successful. Flow diverter stent implant allowed recanalization of the treated vessels (stenosis of 89±10.5% was improved to 26±13%) without procedure related complications. At the 3 month clinical and radiological follow-up, patients either improved or remained stable, and showed stent patency. One patient presented with asymptomatic occlusion of the revascularized artery at 13 months, emphasizing the need for prolonged antiplatelet therapy. CONCLUSIONS: This preliminary series of patients with high risk steno-occlusive lesions affecting tortuous arterial segments or presenting with heavy thrombotic load managed by the implant of flow diverter stents shows that this approach is feasible, safe, and effective in achieving arterial recanalization. Further studies will elucidate the role of this technique in ischemic cerebrovascular settings.

Superficial siderosis of the central nervous system secondary to spinal ependymoma.

Superficial siderosis of the central nervous system is a syndrome caused by deposition of hemosiderin in the subpial layers of the central nervous system, occurring as a result of recurrent asymptomatic or symptomatic bleeding into the subarachnoid space. We report a rare case of superficial siderosis in a 33-year-old man who presented with sensorineural hearing loss. The diagnosis of superficial siderosis on MRI brain studies led to further investigations with detection of a spinal ependymoma at L1-L2, compressing the cauda equina. Gross total resection of the tumor arrested the progression of the neurological deterioration. Our report underlies the importance of early diagnosis and surgical management, with imaging examination of the full neuroaxis to identify the source of bleeding, to halt disease progression and improve prognosis.

In vitro visualization of betaine aldehyde synthesis and oxidation using hyperpolarized magnetic resonance spectroscopy.

Real-time monitoring of betaine aldehyde metabolism at high temporal resolution was accomplished using a hyperpolarized choline analog and (13)C-NMR. This represents the first observation of an aldehyde intermediate on hyperpolarized MR and opens the way for kinetic studies of oxidase/dehydrogenase enzymes in vitro and in vivo.

In vivo magnetic resonance imaging of glucose - initial experience.

A new noninvasive, nonradioactive approach for glucose imaging using spin hyperpolarization technology and stable isotope labeling is presented. A glucose analog labeled with (13)C at all six positions increased the overall hyperpolarized imaging signal; deuteration at all seven directly bonded proton positions prolonged the spin-lattice relaxation time. High-bandwidth (13)C imaging overcame the large glucose carbon chemical shift dispersion. Hyperpolarized glucose images in the live rat showed time-dependent organ distribution patterns. At 8 s after the start of bolus injection, the inferior vena cava was demonstrated at angiographic quality. Distribution of hyperpolarized glucose in the kidneys, vasculature, and heart was demonstrated at 12 and 20 s. The heart-to-vasculature intensity ratio at 20 s suggests myocardial uptake. Cancer imaging, currently performed with (18)F-deoxyglucose positron emission tomography (FDG-PET), warrants further investigation, and glucose imaging could be useful in a vast range of clinical conditions and research fields where the radiation associated with the FDG-PET examination limits its use.

Extraction of a headscarf pin from the vertebral artery without embolization.

BACKGROUND: Foreign bodies traversing the aerodigestive tract lining into the surrounding soft tissues is a well-known entity. A 14-year-old girl was referred to our hospital after swallowing a pin that was not visualized by laryngoscopy, despite a neck film that localized it to the level of the larynx. METHODS: A CT scan demonstrated a bent pin piercing the left vertebral artery "through and through," and this was confirmed by angiography. The pin was extracted via an external approach to the neck without preoperative intravascular manipulation. RESULTS: Angiography immediately after the surgery demonstrated a stable thrombotic sleeve in the vertebral artery without further clot propagation or bleeding from the vessel wall. This is the first report of a "through and through" thrombotic sleeve in an artery. CONCLUSIONS: Simple surgical removal of a sharp foreign body from the vertebral artery without intravascular management may be a reasonable option.