2005 PRETEXT : a revised staging system for primary malignant liver tumours of childhood developed by the SIOPEL group Over the last 15 years , various oncology groups throughout the world have used the PRETEXT system for staging malignant primary liver tumours of childhood . This paper , written by members of the radiology and surgery committees of the International Childhood Liver Tumor Strategy Group -LRB- SIOPEL -RRB- , presents various clarifications and revisions to the original PRETEXT system . Introduction The PRETEXT system was designed by the International Childhood Liver Tumor Strategy Group -LRB- SIOPEL -RRB- for staging and risk stratification of liver tumours -LSB- 1 , 2 -RSB- . PRETEXT is used to describe tumour extent before any therapy , thus allowing more effective comparison between studies conducted by different groups . The system has good interobserver reproducibility -LSB- 3 -RSB- and good prognostic value in children with hepatoblastoma -LSB- 2 -- 5 -RSB- , and is the basis of risk stratification in current SIOPEL hepatoblastoma studies . Most other study groups now use the PRETEXT system to describe imaging findings at diagnosis , even if this is not their main staging system . Certain limitations of the system have become obvious over the last 15 years . In addition , there have been significant advances in imaging during this period -LSB- 6 -RSB- . This paper is the report of a working party that met in June 2005 to update the PRETEXT system . PRETEXT staging is based on Couinaud 's system of segmentation of the liver -LRB- Fig. 1 -RRB- -LSB- 7 -RSB- . The liver segments are grouped into four sections as follows : segments 2 and 3 -LRB- left lateral section -RRB- , segments 4a and 4b -LRB- left medial section -RRB- , segments 5 and 8 -LRB- right anterior section -RRB- and segments 6 and 7 -LRB- right posterior section -RRB- . The term section is used -LRB- where other authors use segment or sector -RRB- to avoid terminological confusion . Fig. 1Schematic representations of the segmental anatomy of the liver . a Frontal view of the liver . The numerals label Couinaud 's segments 2 to 8 . b The hepatic veins -LRB- black -RRB- and the intrahepatic branches of the portal veins -LRB- grey -RRB- are shown . Segment 1 -LRB- equivalent to the caudate lobe -RRB- is seen to lie between the portal vein and the inferior vena cava . c Exploded frontal view of the segmental anatomy of the liver . The umbilical portion of the left portal vein -LRB- LPV -RRB- separates the left medial section from the left lateral section -LRB- LLS -RRB- . Segment 1 is obscured in this view . Note that the term `` section '' has been used in preference to `` segment '' or `` sector '' -LRB- see text -RRB- . d Transverse section of the liver shows the planes of the major venous structures used to determine the PRETEXT number . The hepatic -LRB- blue -RRB- and portal -LRB- purple -RRB- veins define the sections of the liver -LRB- 2 -- 8 -RRB- . This schematic diagram shows how the right hepatic -LRB- RHV -RRB- and middle hepatic -LRB- MHV -RRB- veins indicate the borders of the right anterior section -LRB- RAS -RRB- with the right posterior -LRB- RPS -RRB- and left medial -LRB- LMS -RRB- sections . Note that the left portal vein -LRB- LPV -RRB- actually lies caudal to the confluence of the hepatic veins and is not seen in the same transverse image . The left hepatic vein -LRB- LHV -RRB- runs between segments 2 and 3 and is not used in PRETEXT staging In the original system , the caudate lobe -LRB- segment 1 -RRB- was ignored . The PRETEXT number was derived by subtracting the highest number of contiguous liver sections that were not involved by tumour from four -LSB- 1 -RSB- . This number is , very roughly , an estimate of the difficulty of the expected surgical procedure -LRB- Table 1 -RRB- . Pedunculated tumours are considered to be confined to the liver and to occupy only the section -LRB- s -RRB- from which they originate . Table 1Definitions of PRETEXT number -LRB- see text for PRETEXT number of tumours involving the caudate lobe -RRB- PRETEXT numberDefinitionIOne section is involved and three adjoining sections are freeIIOne or two sections are involved , but two adjoining sections are freeIIITwo or three sections are involved , and no two adjoining sections are freeIVAll four sections are involved In addition to describing the intrahepatic extent of the primary tumour -LRB- s -RRB- , the PRETEXT system includes certain other criteria . These assess involvement of the inferior vena cava -LRB- IVC -RRB- or hepatic veins -LRB- designated V -RRB- , involvement of the portal veins -LRB- P -RRB- , extrahepatic abdominal disease -LRB- E -RRB- and distant metastases -LRB- M -RRB- . The purpose of the 2005 revision was to improve the original definitions of the PRETEXT stages , to clarify the criteria for `` extrahepatic '' disease , and to add new criteria -LRB- Table 2 -RRB- . The term `` extrahepatic '' disease is confusing , and these categories will in future be called `` additional criteria '' . There is still much to be learned about prognostic factors in the primary malignant liver tumours of childhood . An important goal of these changes , therefore , is to improve our ability to identify prognostic imaging findings , and thereby refine risk stratification . Table 22005 PRETEXT staging : additional criteriaCaudate lobe involvementCC1Tumour involving the caudate lobeAll C1 patients are at least PRETEXT IIC0All other patientsExtrahepatic abdominal diseaseEE0 No evidence of tumour spread in the abdomen -LRB- except M or N -RRB- Add suffix `` a '' if ascites is present , e.g. , E0aE1Direct extension of tumour into adjacent organs or diaphragmE2Peritoneal nodulesTumour focalityFF0Patient with solitary tumourF1Patient with two or more discrete tumoursTumour rupture or intraperitoneal haemorrhageHH1Imaging and clinical findings of intraperitoneal haemorrhageH0All other patientsDistant metastasesMM0No metastasesAdd suffix or suffixes to indicate location -LRB- see text -RRB- M1Any metastasis -LRB- except E and N -RRB- Lymph node metastasesNN0No nodal metastasesN1Abdominal lymph node metastases onlyN2Extra-abdominal lymph node metastases -LRB- with or without abdominal lymph node metastases -RRB- Portal vein involvementPP0No involvement of the portal vein or its left or right branchesSee text for definition of involvement . Add suffix `` a '' if intravascular tumour is present , e.g. , P1aP1Involvement of either the left or the right branch of the portal veinP2Involvement of the main portal veinInvolvement of the IVC and/or hepatic veinsVV0No involvement of the hepatic veins or inferior vena cava -LRB- IVC -RRB- See text for definition of involvement . Add suffix `` a '' if intravascular tumour is present , e.g. , V3aV1Involvement of one hepatic vein but not the IVCV2Involvement of two hepatic veins but not the IVCV3Involvement of all three hepatic veins and/or the IVC Although the PRETEXT system is principally used for hepatoblastoma , the 2005 revision is intended to be applicable to all primary malignant liver tumours of childhood , including hepatocellular carcinoma and epithelioid haemangioendothelioma . The original SIOPEL risk stratification system for hepatoblastoma has already been modified in the protocols for current SIOPEL studies -LRB- Table 3 -RRB- . Firstly , tumour rupture or intraperitoneal haemorrhage at the time of diagnosis -LRB- H1 , see below -RRB- is now a defining criterion of high risk . Secondly , children with alpha-fetoprotein levels of < 100 μg/l are also considered to be high risk . The 2005 revision involves no further change in the SIOPEL risk stratification system for hepatoblastoma . Table 3Risk stratification in hepatoblastoma for current SIOPEL studiesHigh riskStandard riskPatients with any of the following : Serum alpha-fetoprotein < 100 μg/lAll other patientsPRETEXT IVAdditional PRETEXT criteria : E1 , E1a , E2 , E2a H1 M1 -LRB- any site -RRB- N1 , N2 P2 , P2a V3 , V3a PRETEXT grouping The traditional approach to radiological segmentation of the liver , based on the paths of the hepatic veins , is an oversimplification . This is partly due to the variability of hepatic venous anatomy -LSB- 8 -- 10 -RSB- . The main problem , however , is the imperfect correlation with segments defined by the branching pattern of the portal veins -LSB- 8 , 11 -- 13 -RSB- . Although the plane of the right hepatic vein reliably separates the right posterior and anterior sections -LSB- 9 -RSB- , the left hepatic vein runs to the left of the boundary between the left lateral and medial sections , which is best defined by the plane of the fissure of the ligamentum teres and the umbilical portion of the left portal vein -LRB- Fig. 1 -RRB- -LSB- 14 -RSB- . PRETEXT I This group includes only a small proportion of primary malignant liver tumours of childhood . From the definition of the PRETEXT number , it can be seen that only tumours localized to either the left lateral section or the right posterior section qualify as PRETEXT I -LRB- Fig. 2 -RRB- . Fig. 2PRETEXT I. a The left lateral section -LRB- segments 2 and 3 -RRB- is involved . b The right posterior section -LRB- segments 6 and 7 -RRB- is involved PRETEXT II Most PRETEXT II tumours are limited to either the right lobe or the left lobe of the liver . Tumours of the left medial or right anterior sections are also PRETEXT II . Multifocal tumours involving only the left lateral and right posterior sections are classified as PRETEXT II ; this pattern is very rare . Tumours limited to the caudate lobe were not classifiable under the original PRETEXT system -LSB- 1 -RSB- . In the 2005 PRETEXT system these tumours are classified as PRETEXT II -LRB- but see also C , below -RRB- . This is the only change in the PRETEXT numbering system in this revision . There is no change in numbering for tumours involving the caudate lobe and any other part of the liver , which are classified as PRETEXT II -LRB- if two or three contiguous sections are free -RRB- , III -LRB- if there are no two contiguous sections free -RRB- or IV -LRB- if all four sections are involved -RRB- -LRB- Fig. 3 -RRB- . Fig. 3PRETEXT II . a Tumour involving only the right lobe of the liver . b A transverse T1-weighted MR image of a child with hepatoblastoma shows that the middle hepatic vein -LRB- arrow -RRB- is displaced but not involved by the tumour . This is the most common type of PRETEXT II tumour . c Tumour involving only the left lobe of the liver . d Tumour involving only the left medial section . e Tumour involving only the right anterior section . f Multifocal tumours involving only the left lateral and right posterior sections . g The tumour is confined to the caudate lobe -LRB- PRETEXT II C1 , see text ; RPV right portal vein -RRB- PRETEXT III The unifocal tumours in this category spare only the left lateral or right posterior section . These tumours are relatively common . In children with hepatoblastoma , great care must be taken to distinguish between invasion and compression of the apparently uninvolved section of the liver , because risk stratification -LRB- and/or the need for liver transplantation -RRB- may depend on this point . Anterior central liver tumours involve segment 4 and either or both of segments 5 and 8 . Although recent advances in surgical technique permit resection of these tumours without trisectionectomy -LSB- 15 -RSB- , classification as PRETEXT III reflects the difficulty of these operations -LRB- Fig. 4 -RRB- . Fig. 4PRETEXT III . a Extensive tumour sparing only the left lateral section . b Extensive tumour sparing only the right posterior section . c Anterior central liver tumour involving the left medial and right anterior sections . d Contrast-enhanced CT image shows a central liver tumour lying between the left portal vein -LRB- white arrow -RRB- and the right hepatic vein -LRB- black arrow -RRB- . e Multifocal PRETEXT III tumour , sparing the right anterior section . f Multifocal tumours sparing only the left lateral and right anterior sections . g Multifocal tumours sparing only the left medial and right posterior sections Multifocal PRETEXT III tumours may also spare the right anterior or left medial sections , or two non-contiguous sections . These patterns are rare . PRETEXT IV PRETEXT IV tumours involve all sections of the liver . These tumours are often multifocal . Alternatively , a very large solitary tumour can involve all four sections -LRB- Fig. 5 -RRB- . Fig. 5PRETEXT IV . a Multifocal PRETEXT IV tumours involve all four sections . b Contrast-enhanced CT image of a patient with PRETEXT IV F1 -LRB- see text -RRB- hepatoblastoma . c Unifocal PRETEXT IV tumours often have a diffuse growth pattern . d Contrast-enhanced CT image of a patient with diffuse PRETEXT IV hepatoblastoma C : caudate lobe tumours The caudate lobe and caudate process -LRB- segment 1 or segments 1 and 9 , depending on the system of nomenclature -RRB- can be resected with either the left or right lobe of the liver -LSB- 7 -RSB- . For this reason , segment 1 was not considered in the PRETEXT classification in the original system -LSB- 2 -RSB- . Modern surgical techniques have made resection of segment 1 safer , but these operations remain difficult . Involvement of the caudate lobe is , therefore , a potential predictor of poor outcome . If any tumour is present in segment 1 on imaging at diagnosis -LRB- Fig. 3g -RRB- , the patient will be coded as C1 , irrespective of the PRETEXT group -LRB- see above -RRB- . All other patients should be coded as C0 . E : extrahepatic abdominal disease The assessment of extrahepatic abdominal disease was one of the most confusing aspects of the original PRETEXT system , and clearly needed revision . Originally , there was a requirement for all extrahepatic abdominal spread of tumour -LRB- E + -RRB- to be proved by biopsy . Modern imaging techniques are capable , in principle , of identifying extrahepatic abdominal tumour extension in many forms . The frequency and significance of these imaging findings is different for different tumour types , and not all patterns are easily biopsied . In hepatoblastoma , for example , direct extension of tumour into other abdominal organs is unusual . Tumour extension through the diaphragm -LRB- Fig. 6 -RRB- is uncommon , but can be shown quite convincingly by MRI or CT , and biopsy proof may be impractical . In the 2005 revision , patients with direct extension of tumour through the diaphragm or into other organs can be coded as E1 without biopsy proof . Fig. 6Extrahepatic abdominal tumour extension . This composite of contrast-enhanced CT images in a patient with hepatoblastoma shows growth of the primary tumour through the diaphragm into the thorax -LRB- E1 -RRB- . The 2005 PRETEXT system no longer requires biopsy proof for this form of tumour spread Pedunculated tumours are considered to be confined to the sections from which they arise , and are not extrahepatic disease . Peritoneal tumour seeding was originally not included in this category -LSB- 2 -RSB- . It probably indicates more advanced abdominal disease than direct extension of the primary tumour . Imaging techniques , especially ultrasonography , can often show even small peritoneal nodules clearly , and the differential diagnosis is very limited . In the 2005 revision , peritoneal nodules will be assumed to be metastases , and will be coded as E2 . All other patients should be coded as E0 . Ascites is an unusual finding at presentation in hepatoblastoma , but is more common in hepatocellular carcinoma , where it may be an independent predictor of poor prognosis . For this reason , patients with ascites will be coded as E0a , E1a or E2a as appropriate . Abdominal lymph node metastases , which were previously recorded as E + , are now coded as N -LRB- see below -RRB- . F : tumour focality In SIOPEL 1 , multifocal tumours were identified at the time of diagnosis in 18 % of the patients with hepatoblastoma where this information was available -LSB- 4 -RSB- . Univariate analysis showed that the 5-year event-free survival was significantly worse for patients with multifocal tumour -LRB- 40 % -RRB- than for those with unifocal tumour -LRB- 72 % -RRB- -LSB- 4 -RSB- . The independent significance of this finding is unclear , as there is clearly an association between multifocality and advanced PRETEXT number . The German Society of Pediatric Oncology and Hematology reported slightly different results -LSB- 16 -RSB- . In its HB89 study , 21 % of patients had multiple well-defined tumours , and these children had a similar disease-free survival -LRB- DFS ; 87 % -RRB- to those with a single tumour -LRB- 86 % -RRB- . However , in 20 % of children the tumour exhibited a diffuse growth pattern -LRB- Fig. 5 -RRB- , and these had a significantly worse DFS -LRB- 21 % -RRB- -LSB- 16 -RSB- . Unfortunately , a diffuse growth pattern is difficult to define , and despite the promise that this finding shows as a potential risk factor , it was decided not to incorporate it in the 2005 PRETEXT revision . Patients with one hepatic tumour should be coded as F0 . All those with more than one tumour nodule -LRB- Figs. 3 , 4 and 5 -RRB- , regardless of nodule size or PRETEXT stage , should be coded as F1 . H : tumour rupture or intraperitoneal haemorrhage It is not uncommon for hepatoblastoma and hepatocellular carcinoma to present with tumour rupture -LSB- 17 , 18 -RSB- . Originally , these patients were not automatically included as high risk in SIOPEL studies , because of the requirement that extrahepatic disease -LRB- E -RRB- be proved by biopsy . Although the data to prove this are not currently available , it seems intuitively likely that tumour rupture -LRB- usually manifesting as intraperitoneal haemorrhage -RRB- is a risk factor , and these patients should be coded as H1 . Laparotomy or aspiration of peritoneal blood is not necessary for diagnostic purposes if characteristic imaging and clinical findings -LRB- such as hypotension and low haematocrit or haemoglobin level -RRB- are present . The presence of peritoneal fluid on imaging alone does not imply tumour rupture -LRB- but see E above -RRB- . Since the opening of the SIOPEL 4 study in September 2004 , tumour rupture has become a defining feature of high-risk hepatoblastoma in SIOPEL studies . Patients with no evidence of tumour rupture or haemorrhage , and those with only subcapsular or biopsy-related intraperitoneal bleeding , are coded as H0 . M : distant metastases Patients with distant metastases at diagnosis are coded as M1 . In hepatoblastoma , these metastases are predominantly found in the lungs . Although the best imaging modality for the identification of lung metastases is currently CT , the defining characteristics of lung metastases in this context have not been specifically studied . It is believed , however , that factors favouring a diagnosis of metastasis include multiple lesions , a rounded , well-defined contour and a subpleural location . In most parts of the world , a single rounded lung lesion with a diameter of > 5 mm in a child with a primary liver tumour is very likely to be a metastasis . Patients with these findings on chest CT scans should be classified as M1 . Biopsy is not required for staging purposes , because it is uncommon for other lesions to mimic metastases in this clinical context . The protocols of the SIOPEL studies recommend central radiological review if there is any doubt about the presence of lung metastases . Other metastases are infrequently found at diagnosis in hepatoblastoma , but are more common in hepatocellular carcinoma . The imaging findings of brain metastases are usually characteristic , and biopsy is not required . Bone scintigraphy is recommended for staging in children with hepatocellular carcinoma , but not hepatoblastoma . Abnormal calcium metabolism is common in children with hepatoblastoma , and may cause abnormal uptake on bone scintigraphy , especially in the ribs -LSB- 19 -RSB- , whereas bone metastases are rare -LSB- 20 -RSB- . Biopsy proof is therefore mandatory for suspected bone metastases in hepatoblastoma , unless the findings of cross-sectional imaging are characteristic and the patient is already in the high-risk category for some other reason , such as the presence of lung metastases . Bone marrow biopsy is not recommended in children with hepatoblastoma , because bone marrow spread is rare -LSB- 20 -RSB- . It is not known whether metastases at different sites have different prognostic implications . For statistical purposes , it is therefore recommended that one or more suffixes be added to M1 to indicate the major sites of metastasis : pulmonary -LRB- p -RRB- , skeletal -LRB- s -RRB- , central nervous system -LRB- c -RRB- , bone marrow -LRB- m -RRB- , and other sites -LRB- x -RRB- . A child with lung , brain , and adrenal metastases would therefore be coded as M1cpx . Patients with no evidence of haematogenous metastatic spread of tumour should be coded as M0 . N : lymph node metastases Because porta hepatis -LRB- and other abdominal -RRB- lymph node metastases are quite unusual in hepatoblastoma , SIOPEL trials have always required this form of tumour spread to be proved by biopsy . In fact , benign enlargement of lymph nodes is probably not uncommon , and the accuracy of positron emission tomography is not known in this context . Because biopsy of equivocal lymph nodes inevitably carries some risk , the SIOPEL committee actively discourages this . Biopsy may , however , be required if there is significant nodal enlargement -LRB- for example short axis > 15 mm -RRB- in a child with no other criteria for high-risk hepatoblastoma . Lymph node metastases are quite common in hepatocellular carcinoma and fibrolamellar carcinoma , and biopsy proof is not required if the imaging abnormality is unequivocal . An arbitrary threshold short axis diameter of 15 mm is suggested for this purpose . Children with no lymph node metastases by these criteria are coded as N0 , those with nodal metastases limited to the abdomen -LRB- i.e. caudal to the diaphragm and cranial to the inguinal ligament -RRB- as N1 , and those with extra-abdominal nodal metastases as N2 . P : portal vein involvement Involvement of the main portal vein and/or both major branches has been considered a risk factor in hepatoblastoma , because this has obvious implications for the resectability of the tumour . It is also possible that portal vein invasion detected by imaging is an independent risk factor for tumour recurrence -LSB- 21 -RSB- . The original PRETEXT criteria , however , did not specifically define the word `` involvement '' . It is well recognized that a tumour that abuts or displaces a major portal venous branch at imaging performed at diagnosis -LRB- Fig. 7 -RRB- may shrink away from the vein following preoperative chemotherapy . Imaging evidence of complete obstruction or circumferential encasement -LRB- Fig. 7 -RRB- is therefore required to qualify as portal vein involvement . Failure to identify the portal vein or one of its major branches in either its normal position or its expected displaced location , on good quality images , is strong evidence of obstruction . The other form of involvement , portal vein invasion , is not uncommon , and is often best detected by ultrasound -LRB- Fig. 7 -RRB- . Various US signs may be present -LSB- 22 , 23 -RSB- , and analogous findings can be seen on CT and MR imaging . Fig. 7Involvement of the portal and hepatic venous systems . a When the tumour -LRB- grey -RRB- approaches or abuts the vein -LRB- black -RRB- , there is no venous involvement , even if the vein is partly encased . b Complete obstruction or encasement of the vein is one form of involvement . Obstruction of the inferior vena cava by extrinsic compression , however , does not count as involvement -LRB- see text -RRB- . c Intravascular tumour growth in the portal and/or hepatic venous systems is not uncommon in children with hepatoblastoma or hepatocellular carcinoma . d Transverse ultrasound image of the right lobe of the liver in a patient with hepatoblastoma . The tumour -LRB- white circles -RRB- has grown into the right branch of the portal vein -LRB- P1a -RRB- , disrupting the normal `` white line '' of the vein wall -LRB- arrows -RRB- Patients with no imaging evidence of involvement of the main portal vein , its bifurcation , or either of its main branches will be coded as P0 . Those who fulfil the original PRETEXT definition of P + -LRB- involvement of the main portal vein , its bifurcation , or both of its main branches -RRB- , as well as those with `` cavernous transformation '' of the portal vein will be coded as P2 . P2 , however , represents very advanced disease . For this reason , the category P1 has been created for patients with evidence of involvement of one major branch of the portal vein . In addition , the detection of portal vein invasion should be marked by the suffix `` a '' -LRB- e.g. , P2a -RRB- . V : involvement of the IVC and/or hepatic veins The same definitions of involvement -LRB- venous obstruction , encasement and/or invasion -RRB- used for the portal veins apply to the hepatic veins -LRB- Fig. 7 -RRB- . A hepatic vein can be assumed to be involved if it can not be identified at all , and its expected course runs through a large tumour mass . It is important to look carefully for the hepatic veins , preferably with ultrasonography as well as CT and/or MRI , as they may be displaced from their expected position by the tumour . Complete obstruction of the IVC can occur with mass effect alone , without any tumour extension to the vein itself . Inability to visualize the IVC , and the presence of an enlarged azygos vein , are not , therefore , sufficient criteria for involvement . Patients with no imaging evidence of involvement of the hepatic veins or IVC will be coded as V0 . As for the portal vein , the original classification of involvement -LRB- V + -RRB- indicated a very advanced level of disease . Intermediate categories have therefore been created . V1 and V2 indicate involvement of one or two main hepatic veins respectively . V3 indicates involvement of either the IVC or all three of the hepatic veins . In addition , the detection of hepatic vein or IVC invasion should be marked by the suffix `` a '' -LRB- e.g. , V2a -RRB- . The presence of tumour in the right atrium automatically makes a patient V3a . SIOPEL risk stratification for patients with hepatoblastoma The SIOPEL risk stratification for children with hepatoblastoma is essentially unchanged by this revision . Patients with any one or more of certain criteria -LRB- Table 3 -RRB- are high risk . All other SIOPEL patients are standard risk . Presurgical re-evaluation Although the timing of surgery will depend on the treatment protocol and the patient 's response to therapy , preoperative reimaging is almost always necessary . All of the PRETEXT categories should be reassessed after preoperative chemotherapy , as near as possible to the time of surgery , and recorded as POSTEXT -LRB- post-treatment extent of disease -RRB- . Comparison of surgical findings with POSTEXT will allow prospective assessment of the accuracy of imaging techniques .

O O O O O B O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O B O O O O B O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O B O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O B O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O B O O O O O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O O O O O O B O O B O O O O O O O B O O B O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O O O O O O O O B B O O O O O O O O O O O O O O O O B B O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O O O O O O O B O O O O O O O B O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O B O O O O O B O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O O O O O O O B O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O B O O O O O O B O O O O O O O B O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O B O B O O O O O O O O O O O O O O B O O O O B O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O B O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O

liver tumour hepatoblastoma staging children


Clinical

and

radiological

features

related

to

the

growth

potential

of

meningioma

Clinical

and

radiological

features

that

help

predict

the

growth

potential

of

meningioma

would

be

beneficial

The

purpose

of

this

study

is

to

clarify

the

characteristics

related

to

proliferating

potential

using

the

staining

index

We

analyzed

the

relationship

of

staining

indices

to

characteristics

of

consecutive

patients

with

meningioma

surgically

removed

between

and

by

logistic

regression

analysis

One

hundred

and

forty-nine

of

the

patients

with

meningioma

were

in

age

male

recurrent

symptomatic

at

the

skull

base

over

multiple

with

edema

with

calcification

The

staining

index

in

of

grade

I

meningiomas

in

WHO

classification

was

in

of

grade

II

and

in

of

grade

III

respectively

Logistic

regression

analysis

demonstrated

that

male

-LRB-

odds

ratio

-LSB-

OR

-RSB-

p

-RRB-

recurrence

-LRB-

OR

p

-RRB-

skull

base

-LRB-

OR

p

-RRB-

calcification

-LRB-

OR

p

-RRB-

were

independent

risk

factors

for

a

high

staining

index

-LRB-

-RRB-

age

symptomatic

volume

multiple

edema

were

not

Male

recurrence

non-skull

base

absence

of

calcification

are

independent

risk

factors

for

a

high

proliferative

potential

These

should

be

taken

into

consideration

when

managing

meningiomas

Introduction

An

estimated

of

the

population

has

an

incidental

asymptomatic

meningioma

in

autopsy

studies

-LSB-

-RSB-

With

the

wider

use

of

CT

and

MRI

many

meningiomas

are

discovered

as

incidental

findings

during

investigation

for

unrelated

symptoms

-LSB-

-RSB-

The

growth

potential

of

meningiomas

varies

Some

meningiomas

remain

unchanged

in

size

for

a

long

period

whereas

others

grow

rapidly

-LSB-

-RSB-

Sex

age

initial

tumor

size

and

calcification

were

reported

to

be

related

to

the

tumor

growth

judging

from

follow-up

scans

-LSB-

-RSB-

The

nuclear

antigen

expressed

by

proliferating

cells

has

become

available

for

routinely

processed

paraffin

section

The

antibody

detects

an

epitope

on

the

antigen

a

nuclear

protein

present

only

during

active

phase

of

the

cell

cycle

-LRB-

S

and

M

-RRB-

-LSB-

-RSB-

Several

studies

investigated

how

labelling

indices

could

help

to

predict

recurrence

-LSB-

-RSB-

An

increased

staining

index

was

highly

correlated

with

a

shorter

tumor

volume

doubling

time

-LSB-

-RSB-

In

the

cases

that

showed

an

of

the

tumor

volume

doubling

time

was

years

Nakaguchi

et

al.

-LSB-

-RSB-

found

the

formula

which

can

calculate

tumor

doubling

time

-LRB-

Td

-RRB-

from

the

staining

index

at

surgery

log

Td

SI

-LRB-

-RRB-

The

time

interval

to

the

next

recurrence

for

recurrent

meningiomas

is

associated

with

the

staining

index

Meningiomas

with

staining

index

of

or

higher

had

a

significantly

higher

tendency

of

recurrence

-LSB-

-RSB-

Although

these

cell

kinetics

methods

are

valuable

for

growth

potential

they

can

be

applied

only

after

the

verification

of

pathology

-LSB-

-RSB-

The

purpose

of

this

study

was

to

clarify

the

clinical

and

radiological

features

related

to

meningioma

proliferation

using

the

staining

index

Sex

age

calcification

edema

symptom

size

and

shape

of

tumor

were

already

reported

to

be

related

to

the

tumor

growth

and

staining

index

-LSB-

-RSB-

The

results

however

were

inconsistent

because

of

a

lack

of

sufficient

case

number

and

inadequate

statistical

analysis

Independent

risk

factors

for

high

growth

rate

should

be

determined

We

analyzed

the

relationship

of

staining

indices

to

the

characteristics

of

consecutive

patients

with

meningioma

surgically

removed

between

and

by

logistic

regression

analysis

Materials

and

methods

Three

hundred

and

forty-two

patients

with

meningiomas

were

surgically

treated

in

our

department

of

neurosurgery

between

and

Radiological

features

were

analyzed

by

CT

scans

and/or

MRI

Location

of

the

tumor

was

classified

as

follows

convexity

falx

parasagittal

sylvian

fissure

tentorial

ventricular

foramen

magnum

olfactory

groove

petroclival

petrous

sphenoid

ridge

and

tuberculum

sellae

The

latter

six

locations

were

considered

as

skull

base

The

tumor

volume

was

calculated

using

the

formula

length

depth

width

-LSB-

-RSB-

When

patients

had

multiple

meningiomas

only

the

largest

tumor

was

included

On

the

basis

of

conventional

CT

and

bone

window

CT

patients

were

divided

into

two

groups

according

to

the

low

density

area

around

the

tumor

and

calcification

in

the

tumor

A

low

density

area

due

to

surgical

scar

was

not

included

in

edema

in

patients

with

recurrent

meningioma

The

tumors

were

histologically

classified

according

to

the

World

Health

Organization

classification

of

tumors

-LSB-

-RSB-

An

avidin-biotin

immunoperoxidase

or

simple

stain

MAX-peroxidase

-LRB-

Nichirei

Tokyo

-RRB-

technique

was

used

to

perform

monoclonal

antibody

-LRB-

DAKO

Denmark

-RRB-

assay

in

selected

sections

of

each

case

All

tissue

sections

were

examined

at

high-power

magnification

-LRB-

-RRB-

The

number

of

cells

stained

positively

with

and

the

total

number

of

tumor

cells

were

counted

in

several

representative

fields

containing

more

than

cells

Their

ratio

was

indicated

as

the

staining

index

-LRB-

-RRB-

Statistical

analysis

All

data

were

stored

on

a

personal

computer

and

analyzed

using

commercially

available

statistical

software

-LRB-

SPSS

version

SPSS

Inc.

-RRB-

Chi-squired

analysis

was

used

to

compare

the

staining

index

to

characteristics

of

patients

with

meningioma

All

variables

were

included

in

a

logistic

regression

model

to

determine

which

variables

were

independently

associated

with

a

high

staining

index

-LRB-

-RRB-

Significance

was

judged

at

a

value

of

p

for

all

analyses

Results

Table

shows

the

characteristics

and

staining

index

of

the

patients

One

hundred

and

forty-nine

of

patients

with

meningioma

were

in

age

male

recurrent

symptomatic

at

the

skull

base

in

volume

multiple

with

edema

with

calcification

We

compare

these

characteristics

to

the

staining

index

We

divided

them

into

two

groups

and

-LSB-

-RSB-

The

staining

index

in

of

meningiomas

was

Sex

-LRB-

p

-RRB-

recurrence

-LRB-

p

-RRB-

symptomatic

-LRB-

p

-RRB-

volume

-LRB-

p

-RRB-

edema

-LRB-

p

-RRB-

and

calcification

-LRB-

p

-RRB-

were

correlated

with

the

staining

index

by

chi-square

test

age

skull

base

and

multiple

were

not

Table

and

staining

index

in

meningiomas

staining

index

-LRB-

-RRB-

Factor

P

ValueAge

-LRB-

years

-RRB-

-LRB-

male/female

-RRB-

Recurrence

-LRB-

yes/no

-RRB-

Symptomatic

-LRB-

yes/no

-RRB-

Skull

base

-LRB-

yes/no

-RRB-

Volume

-LRB-

-RRB-

-LRB-

yes/no

-RRB-

Edema

-LRB-

yes/no

-RRB-

Calcification

-LRB-

yes/no

-RRB-

Meningothelial

transitional

and

fibrous

meningiomas

were

the

three

major

subtypes

and

they

accounted

for

about

three

fourth

of

the

total

Two

hundred

and

ninety-six

meningiomas

belonged

to

grade

I

grade

II

and

grade

III

staining

index

in

of

grade

I

meningiomas

was

that

in

of

grade

II

and

that

in

of

grade

III

respectively

-LRB-

Table

-RRB-

Table

subtypes

and

staining

index

of

staining

index

-LRB-

-RRB-

Total

Grade

IMeningothelial

Logistic

regression

analysis

demonstrated

that

male

-LRB-

odds

ratio

-LSB-

OR

-RSB-

p

-RRB-

recurrence

-LRB-

OR

p

-RRB-

skull

base

-LRB-

OR

p

-RRB-

calcification

-LRB-

OR

p

-RRB-

were

independent

risk

factors

for

a

high

staining

index

-LRB-

-RRB-

age

symptomatic

volume

multiple

and

edema

were

not

-LRB-

Table

-RRB-

Table

regression

analysis

for

factors

independently

related

to

staining

indexFactorOdds

CIP

Skull

Discussion

We

analyzed

the

relationship

of

the

staining

indices

to

the

characteristics

of

consecutive

patients

with

meningioma

surgically

removed

between

and

by

logistic

regression

analysis

Logistic

regression

analysis

demonstrated

that

male

-LRB-

odds

ratio

-LSB-

OR

-RSB-

p

-RRB-

recurrence

-LRB-

OR

p

-RRB-

skull

base

-LRB-

OR

p

-RRB-

calcification

-LRB-

OR

p

-RRB-

were

independent

risk

factors

for

a

high

staining

index

-LRB-

-RRB-

age

symptomatic

volume

multiple

and

edema

were

not

The

relationship

between

the

growth

rate

or

staining

index

and

age

has

been

controversial

a

higher

staining

index

and

higher

growth

rate

were

observed

for

younger

patients

-LSB-

-RSB-

but

not

in

other

reports

-LSB-

-RSB-

Our

series

of

patients

with

meningioma

showed

no

relation

It

is

well

known

that

atypical

and

anaplastic

meningiomas

are

predominant

in

males

-LSB-

-RSB-

Matsuno

et

al.

-LSB-

-RSB-

reported

that

the

mean

staining

index

in

male

patients

was

whereas

that

in

female

patients

was

Our

findings

show

that

male

-LRB-

odds

ratio

-LSB-

OR

-RSB-

p

-RRB-

was

an

independent

risk

factor

for

a

high

staining

index

We

also

found

a

higher

staining

index

in

males

even

in

grade

I

meningioma

-LRB-

staining

index

in

of

females

and

in

of

males

was

p

chi-squire

test

-RRB-

Recurrence

-LRB-

OR

p

-RRB-

was

the

most

significant

independent

risk

factor

for

a

high

staining

index

-LRB-

-RRB-

Therefore

we

propose

prompt

management

for

recurrent

meningiomas

In

most

of

the

recurrent

meningiomas

the

staining

index

was

higher

at

the

time

of

recurrence

than

at

the

time

of

initial

surgery

-LSB-

-RSB-

Changes

in

histological

morphology

and

malignant

transformation

are

also

known

in

meningiomas

Although

there

is

a

significant

difference

in

the

staining

index

between

symptomatic

and

non-symptomatic

meningiomas

by

chi-square

test

symptomatic

is

not

an

independent

risk

factor

for

a

high

staining

index

Meningiomas

commonly

present

with

seizure

disorders

and

are

associated

with

location

perilesional

edema

and

convexity

location

Symptoms

and

signs

of

elevated

intracranial

pressure

could

be

due

to

the

large

size

of

meningioma

itself

or

to

the

pronounced

cerebral

swelling

resulting

from

reactive

vasogenic

edema

Focal

neurological

deficits

caused

by

meningiomas

are

generally

related

to

direct

local

brain

cranial-nerve

compression

and

can

be

predicted

from

the

site

of

origin

of

the

tumor

-LSB-

-RSB-

Thus

symptomatic

meningioma

may

not

be

related

to

a

high

staining

index

The

growth

rate

of

incidental

meningioma

may

be

similar

to

that

of

symptomatic

meningioma

Our

results

demonstrated

that

skull

base

-LRB-

OR

p

-RRB-

is

an

independent

risk

factor

for

a

high

staining

index

No

relationship

has

been

reported

between

the

staining

index

and

the

location

of

meningiomas

-LSB-

-RSB-

In

general

the

surgical

risk

for

meningiomas

is

higher

in

skull

base

A

low

proliferative

potential

in

skull

base

meningiomas

should

be

taken

into

consideration

especially

when

treating

elderly

patients

with

asymptomatic

meningiomas

-LSB-

-RSB-

Although

there

was

a

significant

difference

of

the

staining

index

in

tumor

size

by

chi-square

test

-LSB-

-RSB-

tumor

size

is

not

an

independent

risk

factor

for

a

high

staining

index

The

tumor

volume

is

associated

with

the

annual

growth

rate

but

not

with

doubling

time

-LSB-

-RSB-

Assuming

that

a

tumor

shows

a

constant

relative

volume

increase

larger

tumors

will

show

higher

growth

rates

if

the

annual

volume

increase

is

expressed

in

absolute

values

Large

tumors

should

be

carefully

observed

even

though

the

initial

volume

is

not

a

risk

factor

for

a

high

index

and

it

is

not

correlated

with

doubling

time

The

etiology

of

peritumoral

brain

edema

associated

with

meningiomas

is

multifactorial

Factors

that

may

influence

the

etiology

of

peritumoral

edema

include

tumor

size

histological

subtypes

vascularity

venous

stasis

and

brain

invasion

-LSB-

-RSB-

Ide

et

al.

-LSB-

-RSB-

found

a

significant

correlation

of

both

the

staining

index

and

tumor

size

with

the

extent

of

edema

A

high

staining

index

itself

did

not

seem

to

be

directly

responsible

for

perifocal

edema

since

our

logistic

regression

analysis

demonstrated

that

edema

is

not

an

independent

risk

factor

for

a

high

index

-LSB-

-RSB-

Tumors

with

calcification

grew

significantly

less

than

those

without

calcification

-LSB-

-RSB-

Absence

of

calcification

on

CT

correlated

strongly

with

doubling

time

-LSB-

-RSB-

Diffusely

calcified

meningiomas

had

a

low

mean

staining

index

of

Focally

calcified

tumors

showed

a

relatively

low

proliferative

potential

-LRB-

-RRB-

compared

with

that

of

noncalcified

tumors

-LRB-

-RRB-

-LSB-

-RSB-

The

results

are

always

consistent

when

the

relationship

between

calcification

and

proliferative

potential

or

growth

rate

is

compared

We

also

confirmed

this

characteristic

in

meningioma

-LRB-

OR

p

-RRB-

In

conclusion

male

recurrence

non-skull

base

absence

of

calcification

are

independent

risk

factors

for

a

high

proliferative

potential

These

should

be

taken

into

consideration

when

managing

meningiomas

O O O O O O O B O O B O O O O O O O O B O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O B O O O B O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O


Angiographic CT with intravenous administration of contrast medium is a noninvasive option for follow-up after intracranial stenting Intracranial angioplasty and stenting -LRB- ICAS -RRB- is a therapeutic option in symptomatic intracranial atherosclerotic disease . Adequate follow-up examination is necessary to exclude in-stent restenosis . Conventional intraarterial digital subtraction angiography -LRB- ia-DSA -RRB- is the current gold standard , but it is an invasive technique and carries the risk of neurological complications . Angiographic CT -LRB- ACT -RRB- is a new technique that provides a volume dataset of the highest spatial resolution and high contrast resolution derived from a rotational acquisition of a c-arm-mounted flat-panel detector . The feasibility of ACT with intravenous administration of contrast medium -LRB- iv-ACT -RRB- for follow-up after ICAS is demonstrated . In two patients iv-ACT was performed as a follow-up examination 12 months after ICAS . High-resolution volume data from the rotational acquisitions were processed to provide delineation of the stent lumen as well as imaging of the brain parenchyma and vessels . In both patients the patency of the stent lumen was assessed successfully . In addition , all other brain vessels were displayed in a manner similar to their appearance on CT angiograms . The brain parenchyma was also adequately imaged in a manner similar to its appearance on CT images . We demonstrated the feasibility and diagnostic value of iv-ACT for follow-up imaging after ICAS . This new application has the potential to become the imaging method of choice after ICAS since it not only enables visualization of the patency of the stent lumen but also is minimally invasive and provides additional information about all brain arteries and the brain parenchyma . Introduction In symptomatic intracranial atherosclerotic disease refractive to medical treatment intracranial angioplasty and stenting -LRB- ICAS -RRB- is a therapeutic option increasingly used in specialized stroke centers . However , restenosis rates ranging from 8 % to 30 % have been reported , underlining the necessity for regular follow-up examinations to exclude significant restenosis -LSB- 1 -- 4 -RSB- . CT angiography -LRB- CTA -RRB- and MR angiography -LRB- MRA -RRB- are known to suffer from considerable artifacts that often prevent assessment of the stent lumen . Therefore , current follow-up techniques include transcranial Doppler sonography and conventional intraarterial digital subtraction angiography -LRB- ia-DSA -RRB- . However , diagnostic ia-DSA is an invasive technique with a rate of examination-related neurological complications ranging from 0.5 % to 0.8 % -LSB- 5 , 6 -RSB- . In addition , ia-DSA is not offered on an outpatient basis at every medical center so patients have to be admitted for at least one night , significantly increasing the treatment costs . Furthermore , patient compliance with follow-up examinations may be a problem because the ia-DSA procedure is not very comfortable . The new angiographic systems equipped with flat-panel detectors which allow rotational acquisition of volume data provide the possibility of CT-like low-contrast imaging -LSB- 7 -RSB- . The administration of even highly diluted contrast medium intraarterially gives good delineation of the vessels indicating that intravenous administration of contrast medium could be sufficient . We sought to combine this property with the possibility of nearly artifact-free imaging of small-vessel stents described previously -LSB- 8 -RSB- . Methods DSA and angiographic CT -LRB- ACT -RRB- examinations were performed on an AxiomArtis dBA biplane angiography system equipped with flat panel detectors -LRB- Siemens Medical Solutions , Forchheim , Germany -RRB- . The acquisition of rotational datasets was performed with the following parameters -LRB- 20s-1k protocol -RRB- : 20 s rotation , 538 projections , 220 ° total angle , no zoom -LRB- detector size 30 × 40 cm -RRB- , CTDIweighted approximately 22 mGy -LRB- manufacturer 's information -RRB- . Postprocessing of the image data to a volume dataset -LRB- ACT -RRB- was performed on a Leonardo workstation -LRB- DynaCT , InSpace 3D software , Siemens -RRB- . The software includes the application of system-specific filter algorithms in order to correct for beam hardening , radiation scatter , truncated projections and ring artifacts . Postprocessing resulted in volume datasets each defined by a batch of about 400 slices in a 512 × 512 matrix . Voxel size was about 0.1 × 0.1 × 0.1 mm3 . The ACT datasets were further processed to multiplanar reconstructed -LRB- MPR -RRB- slices with the thin-slice and thick-slice maximum intensity projection -LRB- MIP -RRB- technique parallel and perpendicular to the stent-supplied section of the vessel , respectively . The contrast medium used in the follow-up ACT examination was Imeron 350 -LRB- Bracco ALTANA Pharma , Konstanz , Germany -RRB- . The contrast medium was injected to a volume of 100 ml into a cubital vein at a flow rate of 5 ml/s , and the start delay for rotational acquisition was 20 s . The patient was asked to close his or her eyes and to breathe calmly during the examination . CTA was performed on a 16-slice CT scanner -LRB- Aquilion , Toshiba Medical Systems , Tokyo , Japan -RRB- with 0.5-mm slice collimation , intravenous injection of 60 ml Imeron 350 -LRB- Bracco ALTANA Pharma -RRB- , and a CTDIvol of approximately 50 mGy -LSB- 9 -RSB- . Postprocessing was performed on a Vitrea II workstation -LRB- Vital Systems , Minnetonka , Minn. -RRB- . Case illustrations Case 1 A 57-year old man suffering from brainstem infarction and recurring transient ischemic attacks of the vertebrobasilar circulation was admitted to our hospital . Transcranial ultrasonography and MRA revealed a high-grade stenosis of the basilar artery . The symptoms occurred despite double platelet inhibition -LRB- aspirin and clopidogrel -RRB- and ICAS was chosen as therapy . The procedure was performed under general anesthesia . A balloon-mounted Pharos -LRB- 3.5 / 8 mm -RRB- stent -LRB- Micrus Endovascular , Renens , Switzerland -RRB- was placed and balloon-inflated to a diameter of 3.2 mm thereby reconstructing a diameter corresponding to about 90 % of the normal vessel diameter -LRB- Fig. 1a , b -RRB- . The successful deployment of the stent was documented by native ACT -LRB- Fig. 1c , d -RRB- . No complications occurred after the intervention and the patient was discharged 3 days later . Fig. 1Patient 1 . a , b DSA with selective injection of contrast medium into the right vertebral artery shows the eccentric high-grade stenosis of the basilar artery -LRB- a -RRB- . After stent placement -LRB- b -RRB- the lumen of the basilar artery is well reconstructed and considerable inflow from the contralateral vertebral artery can be seen . c , d Reformatted images in the sagittal plane from an ACT scan directly following the intervention reveal regular deployment of the stent -LRB- c MIP , 0.5-mm slice thickness ; d MIP , 5-mm slice thickness -RRB- An outpatient follow-up CTA was performed 6 months after the procedure . The stent lumen was not adequately visualized on thin-slice MPR -LRB- Fig. 2a -RRB- . Therefore , admission for follow-up DSA was organized for 2 months later . The patient refused ia-DSA , so ACT with intravenous administration of contrast medium -LRB- iv-ACT -RRB- was offered as an alternative . Written informed consent for the examination as a novel application of a rotational acquisition was obtained . The examination was successful . Corresponding to the good low-contrast resolution of ACT described previously , the reconstructed images revealed full patency of the stent lumen -LRB- Fig. 2b , c -RRB- -LSB- 10 -RSB- . This result was highly correlated with the flow-rate measured by transcranial Doppler sonography that had remained normal from directly after the intervention until the 8-month follow-up . Fig. 2Patient 1 . a CTA image obtained at the 6-month follow-up is not of sufficient quality to reveal the stent lumen , and in particular the proximal and distal markers produce substantial artifacts -LRB- MIP , 1-mm slice thickness -RRB- . b , c iv-ACT images obtained at the 8-month follow-up show an unchanged configuration of the stent in comparison to the examination performed directly after the intervention -LRB- see Fig. 1c , d -RRB- . The contrast filling is more faint than on the CTA image but the patency of the stent lumen is visible much more clearly on the sagittal cross sections , and the artifact load is acceptable -LRB- b MIP , 0.5-mm slice thickness ; c MIP , 5-mm slice thickness -RRB- Case 2 An 82-year-old man was admitted suffering from progressive left-sided hemiparesis and impaired consciousness . CTA revealed a high-grade stenosis of the right middle cerebral artery -LRB- MCA -RRB- and a second middle-grade stenosis of the basilar artery -LRB- data not shown -RRB- . CT-perfusion -LRB- CTP -RRB- showed a prolonged mean transit time in the whole right MCA territory but only small infarcted areas level with the basal ganglia , represented by lowered relative cerebral blood volume . Emergency ICAS was performed under general anesthesia . A balloon-mounted Driver -LRB- 2.5 / 8 mm -RRB- stent -LRB- Medtronic , Minneapolis , Minn. -RRB- was successfully placed in the stenosis of the right M1 segment leading to a good morphological result and immediate restoration of normal blood flow -LRB- Fig. 3a , b -RRB- . Proper stent deployment was documented by native ACT -LRB- Fig. 3c , d -RRB- . Fig. 3Patient 2 . a , b DSA images with selective injection into the right internal carotid artery reveals a high-grade stenosis of the right middle cerebral artery -LRB- MCA -RRB- with reduced distal blood flow -LRB- a -RRB- . After stent placement the blood flow is normalized -LRB- b -RRB- . c , d Native ACT reformatted images in paracoronal orientation reveal regular deployment of the stent -LRB- c MIP , 0.5-mm slice thickness ; d MIP , 5-mm slice thickness -RRB- The patient was admitted for follow-up DSA 12 months after the procedure . Transcranial Doppler sonography showed a normal flow velocity in the right MCA . This patient also refused ia-DSA . Written informed consent was obtained in advance to perform iv-ACT and to omit ia-DSA if the iv-ACT was of diagnostic quality . The procedure was performed successfully and the reconstructed images revealed full patency of the stent lumen -LRB- Fig. 4a , b -RRB- . All other intracranial arteries were visible at the highest resolution , revealing an unchanged configuration of the medium-grade stenosis of the basilar artery -LRB- Fig. 4c , d -RRB- . The reconstructed brain parenchyma images showed already known residual infarction -LRB- data not shown -RRB- . Fig. 4Patient 2 . a , b Iv-ACT images obtained 12 months after the intervention reveal an unchanged stent configuration and full patency of the stent lumen -LRB- a MIP , 0.5-mm slice thickness ; b MIP , 10-mm slice thickness -RRB- . Even small perforating arteries originating through the stent struts can be seen -LRB- barrow -RRB- . c A transverse thick-slice -LRB- 30 mm -RRB- MIP overview image gives a good impression of the insular MCA branches of both sides . d A second thick-slice -LRB- 15 mm -RRB- MIP image oriented parallel to the basilar artery reveals a medium-grade stenosis -LRB- arrow -RRB- and an anatomic variant of the origin of the superior cerebellar artery Discussion In patients suffering from intracranial atherosclerosis , ICAS is a promising new therapeutic option -LSB- 1 , 3 , 11 -RSB- . To identify an in-stent restenosis a reliable imaging technique is needed . Here , DSA is the current gold standard , but it carries a 0.5 % to 0.8 % risk of permanent neurological impairment -LSB- 5 , 6 -RSB- . Additionally , not every center is able to perform ia-DSA on an outpatient basis . The risk may be less with ia-ACT if the injection is performed in the aortic arch . However , this is still an invasive procedure . In the study reported here we demonstrated that iv-ACT can reliably depict the lumen of small-vessel stents with high spatial resolution . As the low contrast resolution of ACT is comparable to that of conventional CT , a relatively low concentration of intravascular contrast medium is needed . All intracranial vessels can be viewed simultaneously in a high-quality image . CT-like images of the brain parenchyma are provided as well -LSB- 10 -RSB- . It therefore represents a new radiological imaging technique between CTA and ia-DSA . Even though this new method needs to be evaluated in a larger number of patients , it possibly has many advantages for patients and physicians as a new option in the imaging of cerebrovascular disease : Examinations can be performed on an outpatient basis and the risk of neurological complications is lowered practically to zero . The examination can be performed quickly , in a time similar to that required for a CTA examination . The radiation exposure for the patient from a rotational acquisition is lower than that from a CTA examination -LRB- manufacturer 's information -RRB- and has been shown to be considerably lower than that from a single biplane DSA series -LSB- 12 -RSB- . Possible drawbacks of the iv-ACT technique first include movement artifacts . The patient has to lie nearly motionless for about 20 seconds , which requires a high level of compliance and is not always feasible in patients suffering from cerebrovascular disease . The first stent we examined is a relatively new balloon-mounted stent designed for intracranial use -LRB- Pharos , Micrus Endovascular , Renens , Switzerland -RRB- . All dedicated intracranial stents -LRB- Neuroform and Wingspan , Boston Scientific , Natick , Mass. ; LEO , BALT , Montmorency , France ; and Enterprise , Cordis , Miami Lakes , Fl. -RRB- have a similar strut size of about 0.06 mm -LSB- 13 -RSB- . In contrast , common coronary stents have thicker struts -LRB- e.g. Driver , Medtronic , Minn. : 0.09 mm -RRB- -LSB- 14 -RSB- . Our second patient demonstrates that the lumen of these stents can be visualized as well . This issue is not unimportant because until recently dedicated intracranial stents were not available . Therefore , the majority of stents implanted into intracranial vessels are still coronary stents . Iv-ACT is a promising new technique for minimally invasive follow-up after intracranial stenting . Other possible applications can be envisaged , such as diagnostic and follow-up imaging before and after endovascular treatment of intracranial aneurysms or arteriovenous malformations .

O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O

cerebrovascular disease
intracranial stenting

rotational angiography
angiographic computed tomography
flat-panel