Emerging clinical imaging techniques for cerebral cavernous malformations: a systematic review

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  • 1 Department of Neurosurgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania; and
  • | 2 Neurovascular Surgery Program, Division of Neurosurgery, Biological Sciences Division and the Pritzker School of Medicine, University of Chicago, Illinois
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Cerebral cavernous malformations (CCMs) are divided into sporadic and familial forms. For clinical imaging, T2-weighted gradient-echo sequences have been shown to be more sensitive than conventional sequences. Recently more advanced imaging techniques such as high-field and susceptibility-weighted MR imaging have been employed for the evaluation of CCMs. Furthermore, diffusion tensor imaging and functional MR imaging have been applied to the preoperative and intraoperative management of these lesions. In this paper, the authors attempt to provide a concise review of the emerging imaging methods used in the clinical diagnosis and treatment of CCMs.

Abbreviations used in this paper:

CCM = cerebral cavernous malformation; DT = diffusion tensor; DVA = developmental venous anomaly; GRE = gradient echo; fMR = functional MR; SW = susceptibility-weighted; T2*GRE = T2-weighted GRE.

Cerebral cavernous malformations (CCMs) are divided into sporadic and familial forms. For clinical imaging, T2-weighted gradient-echo sequences have been shown to be more sensitive than conventional sequences. Recently more advanced imaging techniques such as high-field and susceptibility-weighted MR imaging have been employed for the evaluation of CCMs. Furthermore, diffusion tensor imaging and functional MR imaging have been applied to the preoperative and intraoperative management of these lesions. In this paper, the authors attempt to provide a concise review of the emerging imaging methods used in the clinical diagnosis and treatment of CCMs.

Abbreviations used in this paper:

CCM = cerebral cavernous malformation; DT = diffusion tensor; DVA = developmental venous anomaly; GRE = gradient echo; fMR = functional MR; SW = susceptibility-weighted; T2*GRE = T2-weighted GRE.

Cerebral cavernous malformations are present in approximately 0.5% of the population.17,44 These lesions are made up of clusters of deformed vessels, lined by endothelium and filled with blood at various stages of thrombosis.12,20 The annual risk of hemorrhage ranges from 0.7% to 1.1% per lesion per year.44 Typically, patients with single lesions have a sporadic form of the disease, while those with multiple lesions (10%–31% of all cases) often have an autosomal dominant form localizable to the CCM1, CCM2, or CCM3 gene loci.7,18,28,32,45 The hallmark of familial CCM is the presence of multifocal lesions throughout the brain with the appearance of new lesions over time.26 The sporadic form of CCM is often characterized by a solitary lesion (or a cluster of lesions) in association with a DVA.3

Prior to the widespread use of MR imaging, CCMs were thought to be rare entities. Modern MR imaging sequences are highly sensitive for detecting CCMs as well as associated hemorrhage at various stages of thrombosis and reorganization.30 Typically, T2-weighted sequences portray these lesions as areas of mixed signal intensity, with a central complicated core and a peripheral rim of decreased signal intensity.9,16 T2-weighted gradient-echo (T2*GRE) imaging has been promoted as the gold standard MR imaging sequence for both sporadic and familial CCMs.30,54 In the current study, we review the current literature and describe the use of emerging imaging techniques being used for the diagnosis and treatment of this entity.

Methods

The PubMed and MEDLINE databases were searched for publications from 1966 through May 2010 using the MeSH terms “cavernoma,” “cavernous malformation,” “imaging,” “diffusion tensor imaging,” “susceptibility weighted,” “gradient echo,” “functional MR imaging,” “Tesla,” and “high field MR imaging.” The search was limited to articles in the English language and relating to human subjects. Reference sections of recent articles and reviews were reviewed and pertinent articles identified. Initially, relevant articles were retrieved in abstract format. Full-text manuscripts were subsequently obtained for all original articles applicable to the current review. The review was supplemented by work currently in progress at the authors' institutions.

Results and Discussion

Conventional MR Imaging Features of CCM

Conventional MR imaging sequences (T1- and T2-weighted imaging) have been associated with the ability to identify clinically symptomatic CCM lesions with a specificity and sensitivity nearing 100%.42 Many CCMs have a characteristic MR imaging appearance that includes a peripheral ring of hypointensity due to hemosiderin deposition in the surrounding parenchyma from repeated microhemorrhages.43 Some authors describe this manifestation as an imaging appearance associated with a limited differential diagnosis.19 A classification system based on imaging and pathological features has been reported to stratify these heterogeneous lesions.54 Type I lesions are characterized by hyperintensity on both T1- and T2-weighted images (depending on the state of methemoglobin), which is consistent with subacute hemorrhage.16 In Type II malformations, loculated regions of hemorrhage are surrounded by gliosis and hemosiderin-stained brain parenchyma. These CCMs exhibit a mixed–signal intensity core on both T1- and T2-weighted images, with a well-circumscribed hypointense rim on T2-weighted images; these lesions are the classic CCMs, with a “popcorn” appearance and a predilection to produce recurrent symptoms.11 Type III lesions demonstrate a core that is iso- or hypointense on T1-weighted sequences and hypointense on T2-weighted sequences as well as a rim that is hypointense on T2-weighted sequences, compatible with chronic resolved hemorrhage or hemosiderin within and surrounding the lesion. Type IV malformations are minute lesions often seen as punctate hypointense foci on GRE MR images. Pathologically, Type 4 lesions may represent capillary telangiectasias or early-stage CCMs seen frequently in the familial form.33,43,54 The appearance of CCMs may vary by MR imaging sequence as a result of differential magnetic susceptibility of blood products at different ages within the lesion and the surrounding hemosiderin ring (Fig. 1).

Fig. 1.
Fig. 1.

Subtle changes in the appearance of a solitary CCM with different MR imaging sequences, reflecting differential sensitivity of blood breakdown products at different ages, and low flow in dilated cavernous channels. The MR imaging appearance of human CCM lesions, including high-field ex-vivo image correlations with confocal microscopy are presented in detail by Shenkar et al.49

Contrast-enhanced imaging is particularly useful in the diagnostic evaluation of CCM, and in clarifying differential diagnosis. The presence of an associated DVA is more likely to define the nongenetic nonfamilial form of the disease.3,20 Also, the presence of an associated DVA may influence surgical decisions, especially with regard to surgical maneuvers aimed at avoiding injury to the DVA and consequences of venous ischemia. The concept of lesion cure with resection must be tempered when resecting a solitary CCM but leaving behind an overt DVA (which could later contribute to CCM recurrence). Contrast administration may delineate patterns of overt enhancement consistent with pathological conditions other than CCM, particularly tumors (homogeneous enhancement) or arteriovenous malformations (serpiginous enhancement). Finally, punctate enhancement in association with CCMs on contrast-enhanced T1-weighted images, without hemosiderin “blossoming” on T2*GRE sequences, has been suggested to represent capillary telangiectasia, most commonly reported in the pons as well as in the bed of DVAs.40

Diagnosis of CCM: Gradient Echo

Areas of the brain containing hemosiderin-laden tissue demonstrate a more recognizable hypointensity on T2-weighted GRE MR images than either T2-weighted conventional spin echo (SE) or fast spin echo (FSE) MR sequences due to magnetic susceptibility effects.4,8,21,23 As such, T2*-weighted GRE imaging has been recommended as the most sensitive technique to evaluate CCM lesions in both the sporadic and familial forms of the disease.30,54 During an in-depth evaluation of 57 French families with a history of familial CCM, Labauge et al.27 found an approximately 5% probability that conventional MR imaging, without a T2*GRE sequence, would fail to spot a CCM. Furthermore, these authors reported that the mean number of lesions per person was five on standard MR imaging, while on T2*GRE sequences, the mean number of lesions detected was 16 (p < 0.001).27 Other authors have reported a higher sensitivity with T2*GRE when compared with other sequences as well.10,39 In evaluating a 3-generation family with familial CCM, Lehnhardt et al.30 compared standard T1-weighted and T2-weighted SE sequences to T2*GRE sequences and noted a dramatically improved sensitivity with regard to lesion number and disease extension. When evaluating CCMs in association with DVA, the T2*GRE sequences may exclude or better delineate associated CCMs (Fig. 2).

Fig. 2.
Fig. 2.

Multiple MR imaging sequences obtained in a patient presenting with temporal lobe seizures. The T2-weighted sequence (A) illustrates subtle abnormality in the left posterior mesiotemporal region, consistent with nonspecific hemosiderin deposition. The Gd-enhanced T1-weighted image (B) delineates a prominent venous structure with “caput medusae” pattern, associated with the T2 signal, likely suggesting an associated DVA. The T2*GRE image (C) reveals much better delineation of multiple foci of the CCM.

The advantages of T2*GRE must be tempered by the effect of hemosiderin “blossoming,” which effectively increases the apparent size of the CCM lesion. Hence, lesions may appear to extend to a pial or ependymal surface on T2*GRE images, while in fact they are surrounded by several millimeters of normal or simply hemosiderin-stained brain tissue. This is extremely important to realize when planning surgical approaches to lesions in the brainstem or other eloquent or deep-seated locations. Also, T2*GRE sequences often reveal multifocal lesions in elderly patients with hypertension and a history of stroke, and the lesions often are distributed in the same territory as hypertensive angiopathy, and should be differentiated in the clinical context from CCM (Fig. 3). Currently, T2*GRE sequences are considered an essential adjunct to the MR imaging of CCM. They are the method of choice for the sensitivity of detection and diagnosis of CCM, but should be supplemented by other sequences for more precise lesion definition, and by careful differential diagnosis.

Fig. 3.
Fig. 3.

A T2*GRE MR image showing multifocal hemorrhagic lesions in an elderly patient with previous strokes, including recent intracerebral hemorrhages associated with untreated hypertension. The T2*GRE MR imaging sequences revealed multifocal occult tiny hemorrhagic lesions, interpreted as hypertensive angiopathy. These are differentiated from familial CCM disease by the clinical setting and by the clustering of lesions in periventricular areas most vulnerable to hypertensive angiopathy. Conversely, CCM disease is associated with lesions in a volume distribution throughout the brain.

Emerging Concepts in CCM Imaging

High-Field MR Imaging

At present, low-flow vascular malformations, such as CCMs, are most frequently evaluated with standard 1.5-T MR imaging based upon hemosiderin-induced susceptibility effects, which cause signal cancellations visible on T2*GRE sequences.29 With standard imaging techniques, approximately 30% of epilepsy patients are not found to have an underlying lesion; some authors have posited that an improved detection of CCMs could aid in the identification of CCMs (causing cryptogenic seizures) not visualized at 1.5 T.22,46 Several authors have investigated the imaging effects of high-field MR imaging in both experimental and clinical settings.36,38,46,48,49 Shenkar et al.48,49 evaluated ex-vivo human CCMs and murine CCMs by high-resolution MR imaging at 9.4 or 14.1 T. The results obtained using high-field MR imaging results correlated with the histopathological findings obtained using confocal microscopy, confirming the angioarchitecture of CCMs at near histological resolution. Novak et al.36 reported a case of a 55-year-old with a frontal hemorrhage, although at 1.5 Tesla the CCM was not apparent. When closely analyzed, the CCM appeared larger and signal loss was several times greater on 8 T MR images than on 1.5-T images.36 Schlamann et al.46 performed imaging in 10 consecutive CCM patients at 1.5 and 7 T. These authors found one additional hypointensity, which was not visible in the 1.5-T examination, and multiple new small hypointense lesions were detected at 7 T in a patient with familial CCM. However, because of increased susceptibility artifacts, these lesions appeared on average 11% larger in the 7-Tesla images.46 Given that magnetic susceptibility artifact is known to increase with the field strength and is readily captured by T2*GRE, CCMs not readily apparent on 1.5-T MR imaging may become more decisively detectable with higher magnetic field strengths.1,2 Furthermore, these authors assessed lesion prevalence at high field using SW imaging, and at lower field using GRE sequences.46 As a result, it remains unknown if the increased sensitivity reported by those authors is attributable to high field strength per se, or to SW imaging sequences as discussed below.

Susceptibility-Weighted MR Imaging

The CCM lesions contain deoxyhemoglobin and hemosiderin, which causes susceptibility effects and a decrease in signal intensity on T2-weighted sequences. Susceptibility-weighted imaging provides a new mode that is particularly suited for imaging vascular malformations as it is very sensitive to deoxyhemoglobin and iron content.6,53 This sequence is assembled from both magnitude and phase images from a high-resolution, 3D velocity-compensated GRE sequence.41 Currently, this method is believed to be the only imaging method capable of appropriately detecting nonhemorrhagic cavernomas and telangiectasias.38 Lee et al.29 were the first to describe the use of SW imaging for imaging cavernomas. These authors presented a series of 10 patients who underwent both T2-weighted and SW MR imaging and found that not only were the margins of the CCMs better delineated, but SW imaging also revealed 2 additional lesions that were not seen on T2-weighted images.29 Cooper et al.15 reported a case of a 59-year-old familial CCM patient in which SW imaging detected nearly triple the number of lesions compared to the T2*GRE sequences. Pinker et al.38 evaluated 17 patients harboring CCMs with standard 1.5-T MR imaging in comparison with 3-T MR imaging that included the SW imaging sequences. In this series, the 3-T SW MR imaging revealed an additional 7 lesions in 6 patients; however, it is unclear whether these patients had sporadic or familial CCMs. In a recent study, based on 15 patients with familial CCMs and a mean age of 34 years, de Souza et al.16 found the following average number of lesions per patient: 5.7 on T2-weighted imaging; 26.3 on T2*GRE imaging; and 45.6 on SW imaging. Thus the number of lesions seen on SW imaging was 1.7 times higher than that seen on T2*GRE sequences (p = 0.001).16 In the largest study to date, 23 cases were assessed by the senior author (I.A.A.) and colleagues in Montpellier, France, confirming that nearly twice as many lesions were detected by SW imaging as compared with T2*GRE sequences; however, this phenomenon was only observed in the 14 familial cases. In none of 9 patients with solitary CCM or clustered lesions in the bed of a DVA did the SW imaging reveal additional lesions other than those noted on T2*GRE images (Menjot et al., manuscript in preparation). Hence, SW imaging seems to increase the sensitivity of lesion detection in familial multifocal CCM lesions; it does not per se appear to reveal lesion multiplicity that had not been already demonstrated by T2*GRE (Figs. 4 and 5). The SW images are highly sensitive to delineation of associated venous anomalies, and possibly telangiectasias, without the need for contrast enhancement. This feature may be a significant advantage in pregnant patients, those with renal impairment, and patients with allergic reactions to Gd-based contrast agents.

Fig. 4.
Fig. 4.

Representative T2-weighted (A), T2*GRE (B), and SW (C) MR images obtained in a patient with a family history of familial CCM disease, who presented for routine MR imaging screening. The T2 sequences (A) revealed 2 suspected CCM lesions, which were better delineated on T2*GRE sequences. The T2*GRE sequences (B) also suggested perhaps 1 or 2 additional subtle lesions. The SW images (C) revealed many additional lesions throughout the brain.

Fig. 5.
Fig. 5.

Representative T1-weighted (A), T2*GRE (B), and SW (C) MR images obtained in a patient with a solitary sporadic CCM that was discovered incidentally in the workup of an unrelated neoplasm. The T1-weighted contrast-enhanced images (A) revealed a suspected CCM in the right frontal cortex and a subtle abnormal venous prominence superior and medial to the lesion (not shown). The T2*GRE images (B) better delineated the same lesion. The SW sequences (C) revealed no additional lesions, although they also demonstrated the suspected venous anomaly.

While SW imaging is not yet widely available, it is possible that, given the early clinical data suggesting its effectiveness, the technique may be added into the routine imaging assessment of vascular malformations as improvements in software technology allow acquisition and dissemination. These sequences might provide endophenotypic markers of disease burden in familial CCM that should be correlated with disease penetrance and aggressiveness in different individuals and kindreds, and with the response to potential therapeutic interventions.

The ultimate applicability of SW imaging is limited by several factors. First, as with T2*GRE, it is difficult to differentiate small venous structures from small areas of hemorrhage and thrombosis. However, sequential SW imaging before and after Gd administration, could ameliorate this deficiency.31 As previously noted, the higher sensitivity of SW sequences may not apply to sporadic or solitary CCMs, or CCM clusters associated with DVA. While SW imaging has shown greater ability to identify lesions in familial CCM, the necessity to apply this imaging modality to sporadic CCMs has yet to be demonstrated. We are not aware of a case in which a solitary lesion was detected on T2*GRE imaging that was later found to be associated with occult lesion multiplicity on the more sensitive SW imaging (Fig. 5). As such, future studies should specifically address SW imaging sensitivity in cases of sporadic CCM, those associated with DVA, and radiation-induced CCMs.

Finally, the nature of those lesions that are delineated on SW images and remain occult on T2*GRE images remains unclear (Fig. 4). Some may be better resolved in the 3D sequence acquisition of SW imaging, while they may have been diminished by “volume averaging” in the typically 2D acquisition of T2*GRE images. The occult punctate lesions may also represent nonhemorrhagic capillary telangiectasias, often reported in conjunction with CCM, which could also represent precursors to more mature CCMs.5

Imaging in Intraoperative Management

The Use of DT Imaging

Diffusion tensor imaging is an MR imaging technique that may be effectively used to visualize the directionality and orientation of white matter tracts in the brain.37 Diffusion tensor tractography has been effectively used to evaluate the characteristics of the hemosiderin rim surrounding CCMs as well as in surgical planning for the resection of CCM in eloquent areas.11,13,14,35 Cauley et al.11 performed DT tractography in 18 patients with solitary CCMs and found that white matter tracts deviated around the center of CCMs, often passing through the hemosiderin rim. Niizuma et al.35 successfully used DT with fiber tracking to determine the location of the displaced corticospinal tract in the removal of a paraventricular CCM. Chen et al.13,14 have reported the used of DT imaging for the removal of several brainstem lesions including a CCM. They reported that DT fiber tracking revealed the anatomical relationship between the local eloquent tracts and the CCM, thus altering their approach and preventing patient morbidity.14 Several authors speculate that DT imaging may be a useful preoperative evaluation for patients with deep-seated lesions impinging upon white matter tracts.14,35 Thus, the use of DT imaging may enhance the decision-making process in the selection of surgical approaches by providing an enhanced understanding of the relevant functional tracts.

The Use of fMR Imaging

Functional MR imaging has the ability to integrate anatomical and functional information. Preoperatively, this imaging technique has the capacity to provide a useful representation of task-related hemodynamic changes in the associated cortical area as well as the pathology through a single imaging modality.25 An early case report described the successful use of fMR imaging in the preoperative assessment of a left central CCM.34 Thickbroom et al.52 evaluated blood-O2-level–dependent contrast fMR imaging in 3 CCM patients and noted some difficulty in correctly isolating the critical regions of eloquent cortex due to the associated susceptibility effect. Schlosser et al.,47 working with the senior author (I.A.A.), did not report any such difficulty. These authors continue to use fMR imaging in clinical practice, even in patients with recent bleeding (Fig. 6). The data from fMR imaging are often supplemented by intraoperative mapping of sensorimotor cortex by reversal of evoked potential amplitude or direct cortical stimulation.55 Zotta et al.56 used traditional MR imaging and fMR imaging fusion to aid in preoperative planning as well as intraoperative guidance. In this series, the authors achieved greater rates of seizure freedom in the group of patients with CCMs in eloquent areas who underwent surgery with fMR imaging than in the group in whom this modality was not used.56 While fMR imaging has demonstrated a clear benefit over other modalities such as brain mapping or somatosensory evoked potentials for tumors located in primary motor cortex, more comprehensive studies to evaluate this technique in the setting of CCMs are needed.50 Specifically, an improved outcome may be attributed to fMR imaging information, while in fact it was achieved because of a combination of information modalities. In CCM, functional data may affect the surgical route chosen to a lesion, and also the extent of resection of perilesional epileptogenic brain in patients with intractable epilepsy.24,51,56

Fig. 6.
Fig. 6.

Representative CT scan and T2-weighted (B), T1-weighted (C), and functional (D) MR images obtained in a patient who presented with acute onset of left arm and hand paresis. The CT examination (A) revealed focal hemorrhage in the rolandic region. The T2-weighted images (B) revealed a hemorrhagic lesion with surrounding edema, consistent with an acute hemorrhage. The T1-weighted images (C) did not clearly identify the location of sensorimotor structures in relation to the lesion. These were easily outlined by functional MR imaging (D), with zones of activation in response to left hand movement shown in red-orange. The region of functional activation on fMR imaging corresponded to reversal of somatosensory median nerve evoked sensory potential recording on the cortical surface, confirming the location of the rolandic sulcus. A more posterior sulcus was chosen for image-guided transsulcal microsurgical resection of the lesion (blue arrow), which proved to be a CCM, and the resection was accomplished without worsening of motor or sensory function.

Conclusions

Prior to the advent of MR imaging, evaluation of CCMs was limited to diagnostic angiography and CT. Currently, MR imaging is the best imaging method to evaluate CCMs, with T2*GRE sequences being described as the “gold standard.”10,30,54 As the use of more advanced imaging techniques continues to achieve widespread distribution, high-field MR imaging and SW MR imaging are likely to become commonplace for the diagnosis and follow-up of these lesions. Additionally, applications such as DT imaging and fMR imaging may achieve more relevance as intraoperative navigational modalities for the treatment of deep-seated lesions in eloquent areas.

Disclosure

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. IAA is supported by grant from the NIH/NINDS for research on cerebral cavernous malformation, including advanced imaging techniques (R01-NS060748).

Author contributions to the study and manuscript preparation include the following. Conception and design: all authors. Acquisition of data: Campbell, Awad. Analysis and interpretation of data: Yadla, Awad. Drafting the article: Jabbour, Campbell, Yadla. Critically revising the article: all authors. Reviewed final version of the manuscript and approved it for submission: Jabbour, Awad. Administrative/technical/material support: Campbell.

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  • 36

    Novak V, , Chowdhary A, , Abduljalil A, , Novak P, & Chakeres D: Venous cavernoma at 8 Tesla MRI. Magn Reson Imaging 21:10871089, 2003

  • 37

    Pierpaoli C, , Jezzard P, , Basser PJ, , Barnett A, & Di Chiro G: Diffusion tensor MR imaging of the human brain. Radiology 201:637648, 1996

  • 38

    Pinker K, , Stavrou I, , Szomolanyi P, , Hoeftberger R, , Weber M, & Stadlbauer A, et al. : Improved preoperative evaluation of cerebral cavernomas by high-field, high-resolution susceptibility-weighted magnetic resonance imaging at 3 Tesla: comparison with standard (1.5 T) magnetic resonance imaging and correlation with histopathological findings—preliminary results. Invest Radiol 42:346351, 2007

    • Search Google Scholar
    • Export Citation
  • 39

    Porter PJ, , Willinsky RA, , Harper W, & Wallace MC: Cerebral cavernous malformations: natural history and prognosis after clinical deterioration with or without hemorrhage. J Neurosurg 87:190197, 1997

    • Search Google Scholar
    • Export Citation
  • 40

    Pozzati E, , Marliani AF, , Zucchelli M, , Foschini MP, , Dall'Olio M, & Lanzino G: The neurovascular triad: mixed cavernous, capillary, and venous malformations of the brainstem. J Neurosurg 107:11131119, 2007

    • Search Google Scholar
    • Export Citation
  • 41

    Reichenbach JR, & Haacke EM: High-resolution BOLD venographic imaging: a window into brain function. NMR Biomed 14:453467, 2001

  • 42

    Rigamonti D, , Johnson PC, , Spetzler RF, , Hadley MN, & Drayer BP: Cavernous malformations and capillary telangiectasia: a spectrum within a single pathological entity. Neurosurgery 28:6064, 1991

    • Search Google Scholar
    • Export Citation
  • 43

    Rivera PP, , Willinsky RA, & Porter PJ: Intracranial cavernous malformations. Neuroimaging Clin N Am 13:2740, 2003

  • 44

    Robinson JR, , Awad IA, & Little JR: Natural history of the cavernous angioma. J Neurosurg 75:709714, 1991

  • 45

    Sahoo T, , Johnson EW, , Thomas JW, , Kuehl PM, , Jones TL, & Dokken CG, et al. : Mutations in the gene encoding KRIT1, a Krev-1/rap1a binding protein, cause cerebral cavernous malformations (CCM1). Hum Mol Genet 8:23252333, 1999

    • Search Google Scholar
    • Export Citation
  • 46

    Schlamann M, , Maderwald S, , Becker W, , Kraff O, , Theysohn JM, & Mueller O, et al. : Cerebral cavernous hemangiomas at 7 Tesla: initial experience. Acad Radiol 17:36, 2010

    • Search Google Scholar
    • Export Citation
  • 47

    Schlosser MJ, , McCarthy G, , Fulbright RK, , Gore JC, & Awad IA: Cerebral vascular malformations adjacent to sensorimotor and visual cortex. Functional magnetic resonance imaging studies before and after therapeutic intervention. Stroke 28:11301137, 1997

    • Search Google Scholar
    • Export Citation
  • 48

    Shenkar R, , Venkatasubramanian PN, , Wyrwicz AM, , Zhao JC, , Shi C, & Akers A, et al. : Advanced magnetic resonance imaging of cerebral cavernous malformations: part II. Imaging of lesions in murine models. Neurosurgery 63:790798, 2008

    • Search Google Scholar
    • Export Citation
  • 49

    Shenkar R, , Venkatasubramanian PN, , Zhao JC, , Batjer HH, , Wyrwicz AM, & Awad IA: Advanced magnetic resonance imaging of cerebral cavernous malformations: part I. High-field imaging of excised human lesions. Neurosurgery 63:782789, 2008

    • Search Google Scholar
    • Export Citation
  • 50

    Shinoura N, , Yamada R, , Suzuki Y, , Kodama T, , Sekiguchi K, & Takahashi M, et al. : Functional magnetic resonance imaging is more reliable than somatosensory evoked potential or mapping for the detection of the primary motor cortex in proximity to a tumor. Stereotact Funct Neurosurg 85:99105, 2007

    • Search Google Scholar
    • Export Citation
  • 51

    Stavrou I, , Baumgartner C, , Frischer JM, , Trattnig S, & Knosp E: Long-term seizure control after resection of supratentorial cavernomas: a retrospective single-center study in 53 patients. Neurosurgery 63:888897, 2008

    • Search Google Scholar
    • Export Citation
  • 52

    Thickbroom GW, , Byrnes ML, , Morris IT, , Fallon MJ, , Knuckey NW, & Mastaglia FL: Functional MRI near vascular anomalies: comparison of cavernoma and arteriovenous malformation. J Clin Neurosci 11:845848, 2004

    • Search Google Scholar
    • Export Citation
  • 53

    Wycliffe ND, , Choe J, , Holshouser B, , Oyoyo UE, , Haacke EM, & Kido DK: Reliability in detection of hemorrhage in acute stroke by a new three-dimensional gradient recalled echo susceptibility-weighted imaging technique compared to computed tomography: a retrospective study. J Magn Reson Imaging 20:372377, 2004

    • Search Google Scholar
    • Export Citation
  • 54

    Zabramski JM, , Wascher TM, , Spetzler RF, , Johnson B, , Golfinos J, & Drayer BP, et al. : The natural history of familial cavernous malformations: results of an ongoing study. J Neurosurg 80:422432, 1994

    • Search Google Scholar
    • Export Citation
  • 55

    Zhou H, , Miller D, , Schulte DM, , Benes L, , Rosenow F, & Bertalanffy H, et al. : Transsulcal approach supported by navigation-guided neurophysiological monitoring for resection of paracentral cavernomas. Clin Neurol Neurosurg 111:6978, 2009

    • Search Google Scholar
    • Export Citation
  • 56

    Zotta D, , Di Rienzo A, , Scogna A, , Ricci A, , Ricci G, & Galzio RJ: Supratentorial cavernomas in eloquent brain areas: application of neuronavigation and functional MRI in operative planning. J Neurosurg Sci 49:1319, 2005

    • Search Google Scholar
    • Export Citation

Contributor Notes

Address correspondence to: Pascal Jabbour, M.D., Department of Neurosurgery, 909 Walnut Street, 2nd Floor, Philadelphia, Pennsylvania 19107. email: pascal.jabbour@jefferson.edu.
  • View in gallery

    Subtle changes in the appearance of a solitary CCM with different MR imaging sequences, reflecting differential sensitivity of blood breakdown products at different ages, and low flow in dilated cavernous channels. The MR imaging appearance of human CCM lesions, including high-field ex-vivo image correlations with confocal microscopy are presented in detail by Shenkar et al.49

  • View in gallery

    Multiple MR imaging sequences obtained in a patient presenting with temporal lobe seizures. The T2-weighted sequence (A) illustrates subtle abnormality in the left posterior mesiotemporal region, consistent with nonspecific hemosiderin deposition. The Gd-enhanced T1-weighted image (B) delineates a prominent venous structure with “caput medusae” pattern, associated with the T2 signal, likely suggesting an associated DVA. The T2*GRE image (C) reveals much better delineation of multiple foci of the CCM.

  • View in gallery

    A T2*GRE MR image showing multifocal hemorrhagic lesions in an elderly patient with previous strokes, including recent intracerebral hemorrhages associated with untreated hypertension. The T2*GRE MR imaging sequences revealed multifocal occult tiny hemorrhagic lesions, interpreted as hypertensive angiopathy. These are differentiated from familial CCM disease by the clinical setting and by the clustering of lesions in periventricular areas most vulnerable to hypertensive angiopathy. Conversely, CCM disease is associated with lesions in a volume distribution throughout the brain.

  • View in gallery

    Representative T2-weighted (A), T2*GRE (B), and SW (C) MR images obtained in a patient with a family history of familial CCM disease, who presented for routine MR imaging screening. The T2 sequences (A) revealed 2 suspected CCM lesions, which were better delineated on T2*GRE sequences. The T2*GRE sequences (B) also suggested perhaps 1 or 2 additional subtle lesions. The SW images (C) revealed many additional lesions throughout the brain.

  • View in gallery

    Representative T1-weighted (A), T2*GRE (B), and SW (C) MR images obtained in a patient with a solitary sporadic CCM that was discovered incidentally in the workup of an unrelated neoplasm. The T1-weighted contrast-enhanced images (A) revealed a suspected CCM in the right frontal cortex and a subtle abnormal venous prominence superior and medial to the lesion (not shown). The T2*GRE images (B) better delineated the same lesion. The SW sequences (C) revealed no additional lesions, although they also demonstrated the suspected venous anomaly.

  • View in gallery

    Representative CT scan and T2-weighted (B), T1-weighted (C), and functional (D) MR images obtained in a patient who presented with acute onset of left arm and hand paresis. The CT examination (A) revealed focal hemorrhage in the rolandic region. The T2-weighted images (B) revealed a hemorrhagic lesion with surrounding edema, consistent with an acute hemorrhage. The T1-weighted images (C) did not clearly identify the location of sensorimotor structures in relation to the lesion. These were easily outlined by functional MR imaging (D), with zones of activation in response to left hand movement shown in red-orange. The region of functional activation on fMR imaging corresponded to reversal of somatosensory median nerve evoked sensory potential recording on the cortical surface, confirming the location of the rolandic sulcus. A more posterior sulcus was chosen for image-guided transsulcal microsurgical resection of the lesion (blue arrow), which proved to be a CCM, and the resection was accomplished without worsening of motor or sensory function.

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    Novak V, , Chowdhary A, , Abduljalil A, , Novak P, & Chakeres D: Venous cavernoma at 8 Tesla MRI. Magn Reson Imaging 21:10871089, 2003

  • 37

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    • Search Google Scholar
    • Export Citation
  • 39

    Porter PJ, , Willinsky RA, , Harper W, & Wallace MC: Cerebral cavernous malformations: natural history and prognosis after clinical deterioration with or without hemorrhage. J Neurosurg 87:190197, 1997

    • Search Google Scholar
    • Export Citation
  • 40

    Pozzati E, , Marliani AF, , Zucchelli M, , Foschini MP, , Dall'Olio M, & Lanzino G: The neurovascular triad: mixed cavernous, capillary, and venous malformations of the brainstem. J Neurosurg 107:11131119, 2007

    • Search Google Scholar
    • Export Citation
  • 41

    Reichenbach JR, & Haacke EM: High-resolution BOLD venographic imaging: a window into brain function. NMR Biomed 14:453467, 2001

  • 42

    Rigamonti D, , Johnson PC, , Spetzler RF, , Hadley MN, & Drayer BP: Cavernous malformations and capillary telangiectasia: a spectrum within a single pathological entity. Neurosurgery 28:6064, 1991

    • Search Google Scholar
    • Export Citation
  • 43

    Rivera PP, , Willinsky RA, & Porter PJ: Intracranial cavernous malformations. Neuroimaging Clin N Am 13:2740, 2003

  • 44

    Robinson JR, , Awad IA, & Little JR: Natural history of the cavernous angioma. J Neurosurg 75:709714, 1991

  • 45

    Sahoo T, , Johnson EW, , Thomas JW, , Kuehl PM, , Jones TL, & Dokken CG, et al. : Mutations in the gene encoding KRIT1, a Krev-1/rap1a binding protein, cause cerebral cavernous malformations (CCM1). Hum Mol Genet 8:23252333, 1999

    • Search Google Scholar
    • Export Citation
  • 46

    Schlamann M, , Maderwald S, , Becker W, , Kraff O, , Theysohn JM, & Mueller O, et al. : Cerebral cavernous hemangiomas at 7 Tesla: initial experience. Acad Radiol 17:36, 2010

    • Search Google Scholar
    • Export Citation
  • 47

    Schlosser MJ, , McCarthy G, , Fulbright RK, , Gore JC, & Awad IA: Cerebral vascular malformations adjacent to sensorimotor and visual cortex. Functional magnetic resonance imaging studies before and after therapeutic intervention. Stroke 28:11301137, 1997

    • Search Google Scholar
    • Export Citation
  • 48

    Shenkar R, , Venkatasubramanian PN, , Wyrwicz AM, , Zhao JC, , Shi C, & Akers A, et al. : Advanced magnetic resonance imaging of cerebral cavernous malformations: part II. Imaging of lesions in murine models. Neurosurgery 63:790798, 2008

    • Search Google Scholar
    • Export Citation
  • 49

    Shenkar R, , Venkatasubramanian PN, , Zhao JC, , Batjer HH, , Wyrwicz AM, & Awad IA: Advanced magnetic resonance imaging of cerebral cavernous malformations: part I. High-field imaging of excised human lesions. Neurosurgery 63:782789, 2008

    • Search Google Scholar
    • Export Citation
  • 50

    Shinoura N, , Yamada R, , Suzuki Y, , Kodama T, , Sekiguchi K, & Takahashi M, et al. : Functional magnetic resonance imaging is more reliable than somatosensory evoked potential or mapping for the detection of the primary motor cortex in proximity to a tumor. Stereotact Funct Neurosurg 85:99105, 2007

    • Search Google Scholar
    • Export Citation
  • 51

    Stavrou I, , Baumgartner C, , Frischer JM, , Trattnig S, & Knosp E: Long-term seizure control after resection of supratentorial cavernomas: a retrospective single-center study in 53 patients. Neurosurgery 63:888897, 2008

    • Search Google Scholar
    • Export Citation
  • 52

    Thickbroom GW, , Byrnes ML, , Morris IT, , Fallon MJ, , Knuckey NW, & Mastaglia FL: Functional MRI near vascular anomalies: comparison of cavernoma and arteriovenous malformation. J Clin Neurosci 11:845848, 2004

    • Search Google Scholar
    • Export Citation
  • 53

    Wycliffe ND, , Choe J, , Holshouser B, , Oyoyo UE, , Haacke EM, & Kido DK: Reliability in detection of hemorrhage in acute stroke by a new three-dimensional gradient recalled echo susceptibility-weighted imaging technique compared to computed tomography: a retrospective study. J Magn Reson Imaging 20:372377, 2004

    • Search Google Scholar
    • Export Citation
  • 54

    Zabramski JM, , Wascher TM, , Spetzler RF, , Johnson B, , Golfinos J, & Drayer BP, et al. : The natural history of familial cavernous malformations: results of an ongoing study. J Neurosurg 80:422432, 1994

    • Search Google Scholar
    • Export Citation
  • 55

    Zhou H, , Miller D, , Schulte DM, , Benes L, , Rosenow F, & Bertalanffy H, et al. : Transsulcal approach supported by navigation-guided neurophysiological monitoring for resection of paracentral cavernomas. Clin Neurol Neurosurg 111:6978, 2009

    • Search Google Scholar
    • Export Citation
  • 56

    Zotta D, , Di Rienzo A, , Scogna A, , Ricci A, , Ricci G, & Galzio RJ: Supratentorial cavernomas in eloquent brain areas: application of neuronavigation and functional MRI in operative planning. J Neurosurg Sci 49:1319, 2005

    • Search Google Scholar
    • Export Citation

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