Four dimensional computed tomography angiography

Four dimensional computed tomography angiography

Intracranial vascular malformations can be detected with 4D-CTA and clinically evaluated using information related to vascular fluid dynamics. The use of 4D-CTA provides data related to ongoing vascular changes as well as accurate spatial delineation of cerebrovascular pathologies. Overall, 4D-CTA is increasing its role in neuroimaging by providing superior information regarding structural three-dimensional imaging quality and real-time flow 1).

Mizutani et al. retrospectively analyzed 97 veins from 26 patients (16 cases of arteriovenous shunt disease, nine intracranial tumor cases, and one cerebral aneurysm case) who underwent both 4D-CTA and conventional digital subtraction angiography (DSA). Using 4D-CTA, they analyzed the time-density curve with gamma distribution extrapolation and obtained the direction of the flow and flow velocity of each vein. The direction of the flow in 4D-CTA was also collated with that obtained using conventional DSA to verify the experimental method.

The direction of the flow determined by 4D-CTA was consistent with that of conventional DSA in 94.8% of cases. The average venous flow velocity was 64.3 mm/s and 81.8 mm/s, respectively, in the antegrade and retrograde channels affected by arteriovenous shunts.

The current flow analysis using 4D-CTA enabled to evaluate the direction and velocity of intracranial venous flow. Aside from some limitations, the current method is reliable and its potential for application in clinical settings is promising 2).

A total of 44 patients with cerebral aneurysm, treated using clipping surgery, were included in this study. The metal artifact volume was assessed using CTA and the association between the type of clips and its metal artifact volume was analyzed. A VR image and a 4D-CTA were then produced, and the diagnostic accuracy of arteries around the clip or residual aneurysm on these images was evaluated. In the receiver operating characteristic (ROC) curve analysis, the cutoff value for metal artifacts was 2.32 mm3 as determined through a VR image. Patients were divided into two groups. Group 1 included patients with a simple and small clip, and group 2 included patients with multiple, large or fenestrated clips. The metal artifact volume was significantly larger in group 2, and the group incorporated the cutoff value. Post-clipping status on the VR image was significantly superior in group 1 compared with group 2. In group 2, the imaging quality of post-clipping status on 4D-CTA was superior in 92.9% of patients. The metal artifact volume was dependent on the number, size, or configuration of the clip used. In group 2, evaluation using a 4D-CTA eliminated the effect of the metal artifacts 3).

Two patients with intracerebral hemorrhage both showed an assumed spot sign on CTA, suggesting active hemorrhage. Additional 4D-CTA showed true active hemorrhage in one patient and a distal intracranial aneurysm in the other. This aneurysm was initially falsely interpreted as a spot sign on conventional CTA.

This case findings show how 4D-CTA can discern active bleeding from aneurysmal hemorrhage in cases with hemorrhagic stroke. This finding proves the additional value of this relatively new technique, because the detected underlying disorders have different therapeutic consequences in the acute setting 4).

In the diagnostic process of spinal VMs, the position of 4D-CTA is the third choice for noninvasive angiography, after dynamic MRA and three-dimensional CTA. However, the role of 4D-CTA might be decisive in difficult-to-find spinal dural AVFs. We believe that this novel imaging technique can be applied in spinal VMs 5).

Alnemari et al. presented 6 cases that best elucidate the application and technical nuances of 4D-CTA and its advantages over traditional digital subtraction angiography.

Intracranial vascular lesions can be detected with 4D-CTA and clinically evaluated using information related to vascular flow dynamics. The use of 4D-CTA provides data related to ongoing vascular changes as well as accurate spatial delineation of cerebrovascular pathologies. Overall, 4D-CTA is increasing its role in neuroimaging by providing superior information regarding structural three-dimensional imaging quality and real-time flow 6).

Ye et al. reported 16 patients who were diagnosed to have intracranial DAVF by digital subtraction angiography (DSA). The 4D-CTA was performed by Aquilion ONE multi-detector CT scanner (Toshiba Medical Systems, Japan) equipped with 320 × 0.5 mm detector rows. Standard biplane fluoroscopy equipments (Infinix, Toshiba Medical Systems, Japan and ADVANTX LC/LP, GE Medical Systems, Milwaukee, WI, USA) were applied in the diagnosis of intra-arterial DSA. Examinations were performed to evaluate the findings of DSA and 4D-CTA in each patient. The examination results were read by two independent readers in a blind manner. All results were documented on standardized scoring sheets. In all 16 cases, the same diagnosis results of intracranial DAVF were obtained from DSA and 4D-CTA. The results of subtype (Borden and Cognard classification), venous reflux and fistula sites were also accurately exhibited in 4D-CTA. In addition, there was a little discrepancy in identifying smaller and specific arterial branches and in distinguishing fistula type (focal or diffuse) using 4D-CTA. Good-to-excellent agreements were made between 4D-CTA and DSA. Therefore, 4D-CTA could be a feasible tool for the characterization of intracranial DAVF, with respect to determining fistula site and venous drainage 7).

A retrospective review was made to assess the accuracy of 4D-CTA) in diagnosis of arteriovenous malformations (AVM) and dural arteriovenous fistulas (DAVF), with catheter-based digital-subtraction angiogram (DSA) being gold standard. 33 pairs of investigations (DSA and 4D-CTA) were performed primarily for suspicion of AVM/DAVF. Based on blinded reports, sensitivity and specificity for detection of AVM/DAVF were 77% (95% CI: 46-95%) and 100% (95% CI: 83-100%) respectively. Positive predictive value was 100% (95% CI: 69-100%) and negative predictive value 87% (95% CI: 66-97%). 4D-CTA is a practical minimally-invasive technique for evaluating cerebrovascular pathologies. There is good agreement between the findings of 4D-CTA and DSA despite the differences in temporal and spatial resolutions. 4D-CTA may obviate the need for DSA in a subgroup of patients who would otherwise have undergone this invasive investigation, which carries a risk of important complications 8).


1) , 6)

Alnemari A, Mansour TR, Bazerbashi M, Buehler M, Schroeder J, Gaudin D. Dynamic Four-Dimensional Computed Tomography Angiography for Neurovascular Pathologies. World Neurosurg. 2017 Sep;105:1034.e11-1034.e18. doi: 10.1016/j.wneu.2017.06.022. Epub 2017 Jun 12. PubMed PMID: 28619493.

Mizutani K, Arai N, Toda M, Akiyama T, Fujiwara H, Jinzaki M, Yoshida K. A novel flow dynamics study of the intracranial veins using whole brain 4D-CTA. World Neurosurg. 2019 Jul 19. pii: S1878-8750(19)32015-7. doi: 10.1016/j.wneu.2019.07.109. [Epub ahead of print] PubMed PMID: 31330333.

Kimura Y, Mikami T, Miyata K, Suzuki H, Hirano T, Komatsu K, Mikuni N. Vascular assessment after clipping surgery using four-dimensional CT angiography. Neurosurg Rev. 2018 Mar 3. doi: 10.1007/s10143-018-0962-0. [Epub ahead of print] PubMed PMID: 29502322.

de Jong JP, Kluijtmans L, van Amerongen MJ, Prokop M, Boogaarts HD, Meijer FJA. “On the Spot”: The Use of Four-Dimensional Computed Tomography Angiography to Differentiate a True Spot Sign From a Distal Intracranial Aneurysm. World Neurosurg. 2017 Sep;105:1037.e9-1037.e12. doi: 10.1016/j.wneu.2017.06.046. Epub 2017 Jun 16. PubMed PMID: 28625908.

Yamaguchi S, Takemoto K, Takeda M, Kajihara Y, Mitsuhara T, Kolakshyapati M, Mukada K, Kurisu K. The Position and Role of Four-Dimensional Computed Tomography Angiography in the Diagnosis and Treatment of Spinal Arteriovenous Fistulas. World Neurosurg. 2017 Jul;103:611-619. doi: 10.1016/j.wneu.2017.03.100. Epub 2017 Mar 30. PubMed PMID: 28366753.

Ye X, Wang H, Huang Q, Jiang M, Gao X, Zhang J, Zhou S, Lin Z. Four-dimensional computed tomography angiography is valuable in intracranial dural arteriovenous fistula diagnosis and fistula evaluation. Acta Neurol Belg. 2015 Sep;115(3):303-9. doi: 10.1007/s13760-014-0387-7. Epub 2014 Oct 30. PubMed PMID: 25354667.

Biswas S, Chandran A, Radon M, Puthuran M, Bhojak M, Nahser HC, Das K. Accuracy of four-dimensional CT angiography in detection and characterisation of arteriovenous malformations and dural arteriovenous fistulas. Neuroradiol J. 2015 Aug;28(4):376-84. doi: 10.1177/1971400915604526. Epub 2015 Oct 1. PubMed PMID: 26427892; PubMed Central PMCID: PMC4757303.

Spinal myxopapillary ependymoma outcome

Spinal myxopapillary ependymoma outcome

Telomerase reverse transcriptase gene promoter (TERTp) mutation has been identified in a subset of ependymomas with aggressive behavior 1).

Despite its benign biological nature, myxopapillary ependymoma (MPE) has a propensity to recur locally or distantly. Although variables influencing the prognosis, such as age, the extent of resection and radiotherapy, have been widely discussed, no definitive standard has been established.

Compared to other spinal tumors, many fewer histological markers have been elucidated to assist the determination of the prognosis.

Treatment failure of MPE occurred in approximately one-third of patients. The observed recurrence pattern of primary spinal MPE was mainly local, but a substantial number of patients failed nonlocally. Younger patients and those not treated initially with adjuvant RT or not undergoing gross total resection were significantly more likely to present with tumor recurrence/progression 2).

The 5-year survival rate of spinal ependymomas ranges from 57–100% 3) 4) 5) and 10–33% of patients will experience local invasion of the tumour or recurrence 6) 7).

Metastasis is rare in MPE but there have been several reported cases 8) 9) 10) 11) 12) 13) 14) 15) 16) 17) 18) 19) 20).



Deniel A, Marguet F, Beaussire L, Tobenas-Dujardin AC, Peillon C, Gambirasio MA, Veresezan O, Magne N, Di Fiore F, Laquerrière A, Sarafan-Vasseur N, Fontanilles M. TERTp mutation detection in plasma by droplet-digital PCR in spinal myxopapillary ependymoma with lung metastases. World Neurosurg. 2019 Jul 19. pii: S1878-8750(19)32017-0. doi: 10.1016/j.wneu.2019.07.111. [Epub ahead of print] PubMed PMID: 31330336.

Weber DC, Wang Y, Miller R, Villà S, Zaucha R, Pica A, Poortmans P, Anacak Y, Ozygit G, Baumert B, Haller G, Preusser M, Li J. Long-term outcome of patients with spinal myxopapillary ependymoma: treatment results from the MD Anderson Cancer Center and institutions from the Rare Cancer Network. Neuro Oncol. 2015 Apr;17(4):588-95. doi: 10.1093/neuonc/nou293. Epub 2014 Oct 9. PubMed PMID: 25301811; PubMed Central PMCID: PMC4483075.

Volpp PB, Han K, Kagan AR, Tome M. Outcomes in treatment for intradural spinal cord ependymomas. Int J Radiation Oncology Biol Phys. 2007;69:1199–1204.
4) , 7)

Hanbali F, Fourney DR, Marmor E, et al. Spinal cord ependymoma: Radical surgical resection and outcome. Neurosurgery. 2002;51:1162–74.

Asazuma T, Toyama Y, Suzuki N, et al. Ependymomas of the spinal cord and cauda equine: An analysis of 26 cases and a review of the literature. Spinal Cord. 1999;37:753–59.

Bavbek M, Altinors MN, Caner HH, Bilezikci B, Agildere M. Lumbar myxopapillary ependymoma mimicking neurofibroma. Spinal Cord. 2001;39:449–452.

Friedman DP, Hollander MD. Neuroradiology case of the day. Radiographics. 1998;18:794–98. [PubMed] 17. Patterson RH, Jr, Campbell WG, Jr, Parsons H. Ependymoma of the cauda equina with multiple visceral metastases. J Neurosurg. 1961;18:145–150.

Agapitos E, Kavantzas N, Karaitianos J, Davaris P. Subcutaneous sacrococcygeal myxopapillary ependymoma: a case report. Archives d’anatomie et de cytologie pathologiques. 1995;43:157–159.

Al Moutaery K, Aabed MY, Ojeda VJ. Cerebral and spinal cord myxopapillary ependymomas: a case report. Pathology. 1996;28:373–376.

Helwig EB, Stern JB. Subcutaneous sacrococcygeal myxopapillary ependymoma: a clinicopathologic study of 32 cases. Am J Clin Pathol. 1994;81:156–161.

Ilhan I, Berberoglu S, Kutluay L, Maden HA. Subcutaneous sacrococcygeal myxopapillary ependymoma. Medical and Pediatric Oncology. 1998;30:81–84.

Kline MJ, Kays DW, Rojiani AM. Extradural myxopapillary ependymoma: report of two cases and review of the literature. Pediatric Pathology and Laboratory Medicine. 1996;6:813–822.

Kramer GW, Rutten E, Sloof J. Subcutaneous sacrococcygeal ependymoma with inguinal lymph node metastasis. J Neurosurg. 1988;68:474–477.

Pulitzer DR, Martin PC, Collins PC, et al. Subcutaneous sacrococcygeal (“myxopapillary”) ependymal rests. Am J Surgical Pathology. 1988;12:672–677.

Woesler B, Moskopp D, Kuchelmeister K, et al. Intracranial metastasis of a spinal myxopapillary ependymoma. A case report. Neurosurgery Review. 1998;21:62–65.

Graf M, Blaeker H, Otto HF. Extraneural metastasizing ependymoma of the spinal cord. Pathology Oncology Research. 1999;5:56–60.

Mavroudis C, Townsend JJ, Wilson CB. A metastasizing ependymoma of the cauda equine: case report. J Neurosurg. 1977;47:771–775.

Rubinstein LJ, Logan WJ. Extraneural metastases in ependymoma of the cauda equina. J Neurol Neurosurg Psychiatry. 1970;33:763–770.

Rickert CH, Kedziora O, Gullotta F. Ependymoma of the cauda equine. Acta Neurochir. 1999;141:781–2.

Flow 800

Flow 800

Indocyanine green (ICG) video angiography (VAG) is an established method for assessment of cerebral blood flow during microsurgical clipping of intracranial aneurysms. FLOW 800 is a surgical microscope-integrated software program that displays the cerebral blood flow in color-coded maps, thus providing semi-quantitative and real-time analysis of ICG data.


This process helps identify early arterialized veins and their flow status during AVM and dAVF surgery and can confirm adequate relative flow within branching vessels during aneurysm surgery when clip-induced stenosis is suspected 1).

Although its role is limited in deep-seated AVMs, if properly dissected and exposed it can give useful information which can be easily interpretable and reproducible 2).


Case series

Goertz et al. retrospectively reviewed 54 patients (mean age: 53.6 ± 11.6 years) that underwent microsurgical clipping for 60 aneurysms and intraoperative evaluation of ICG fluorescence dynamics using FLOW 800 color coded maps. FLOW 800 data were correlated with patient characteristics, clinical outcomes and intraoperative decision-making.

There were no significant differences in FLOW 800 data between ruptured and unruptured aneurysms (p>0.05). Likewise, the hemodynamic parameters were not significantly different before and after definite clip placement (p>0.05). However, in two cases, analysis of transit times by FLOW 800 analysis revealed a hemodynamically significant clip stenosis that might have been missed by conventional ICG-VAG and resulted in adjustment of the clip position. Overall, there was one cerebral infarction, which was not related to clip placement.

FLOW 800 is a useful adjunct to ICG-VAG for intraoperative assessment of cerebral perfusion and may help to identify hemodynamically relevant clip stenosis. The beneficial impact of FLOW 800 on clinical outcome after microsurgical clipping needs to be confirmed by comparative studies 3).

Shah et al. retrospectively reviewed 23 consecutive patients for whom FLOW 800 ICG videoangiography was used. They harbored aneurysms, arteriovenous malformations (AVMs), dural arteriovenous fistula (dAVF), or hemangioblastoma. Patients’ characteristics, FLOW 800 data, and clinical findings were recorded. Color map data were readily available intraoperatively and guided surgery.

The cohort included 10 patients with AVMs, 11 with aneurysms, 1 with dAVF, and 1 with hemangioblastoma. Approximately two thirds of patients underwent intraoperative angiography. FLOW 800 data provided semiquantitative data regarding localization, flow status in major feeding arteries, and dominance of the arterialized draining veins for AVMs, more than data from ICG videoangiography alone. For complex aneurysms, color maps confirmed relative adequate flow in parent and branching vessels. For the foramen magnum dAVF, the location of the dominant transdural connection was appreciated only via flow analysis. Flow analysis created the blood flow map of a large complex solid brainstem hemangioblastoma and guided devascularization. All FLOW 800 findings agreed with intraoperative and postoperative angiography.

ICG videoangiography with FLOW 800 analysis can provide semiquantitative and relative flow magnitude data that are efficient and noninvasive. This process helps identify early arterialized veins and their flow status during AVM and dAVF surgery and can confirm adequate relative flow within branching vessels during aneurysm surgery when clip-induced stenosis is suspected 4).


1) , 4)

Shah KJ, Cohen-Gadol AA. The Application of FLOW 800 ICG Videoangiography Color Maps for Neurovascular Surgery and Intraoperative Decision Making. World Neurosurg. 2018 Oct 5. pii: S1878-8750(18)32250-2. doi: 10.1016/j.wneu.2018.09.195. [Epub ahead of print] PubMed PMID: 30292668.

Kato Y, Jhawar SS, Oda J, Watabe T, Oguri D, Sano H, Hirose Y. Preliminary evaluation of the role of surgical microscope-integrated intraoperative FLOW 800 colored indocyanine fluorescence angiography in arteriovenous malformation surgery. Neurol India. 2011 Nov-Dec;59(6):829-32. doi: 10.4103/0028-3886.91359. PubMed PMID: 22234193.

Goertz L, Hof M, Timmer M, Schulte AP, Kabbasch C, Krischek B, Stavrinou P, Reiner M, Goldbrunner R, Brinker G. Application of intraoperative FLOW 800 ICG videoangiography colour coded maps for microsurgical clipping of intracranial aneurysms. World Neurosurg. 2019 Jul 19. pii: S1878-8750(19)32019-4. doi: 10.1016/j.wneu.2019.07.113. [Epub ahead of print] PubMed PMID: 31330337.
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