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Applications of 3D CISS sequence for problem solving in neuroimaging

Three-dimensional (3D) constructive interference in steady state (CISS) is a gradient-echo MRI sequence that is used to investigate a wide range of pathologies when routine MRI sequences do not provide the desired anatomic information. The increased sensitivity of the 3D CISS sequence is an outcome of the accentuation of the T2 values between cerebrospinal fluid (CSF) and pathological structures. Apart from its well-recognized applications in the evaluation of the cranial nerves, CSF rhinorrhea and aqueduct stenosis, we have found the CISS sequence to be useful for the cisternal spaces, cavernous sinuses and the ventricular system, where it is useful for detecting subtle CSF-intensity lesions that may be missed on routine spin-echo sequences. This information helps in the management of these conditions. After a brief overview of the physics behind this sequence, we illustrate its clinical applications with representative cases and discuss its potential role in imaging protocols.


Physics
A steady-state sequence is a type of gradient-echo sequence in which residual transverse magnetization is refocused so that a steady magnitude of longitudinal and transverse magnetization is achieved after a few repetition time (TR) periods. Once steady state is reached, two types of signals -free induction decay (S+) and spin-echo (S−) -are produced. [2] Balanced-Steady State Free Precission (SSFP) sequence (TrueFISP on Siemens, FIESTA on GE and balanced TFE on Philips) uses both signals (S+ and S−) for image formation. CISS is a modification of TrueFISP. Two consecutive runs of 3D balanced steady-state free precession, one with alternating +α and −α excitation pulses (where α = flip angle) and the other with constant α pulses, are combined. These two image sets show reciprocally shifted 'banding artifacts.' The banding artifact-free CISS image is obtained by the maximum intensity projection between these two data sets. [3] (Avanto-SQ Engine; Siemens, Erlangen, Germany). A 12-channel phased-array head coil and a spine-array surface coil were used. The CISS sequence parameters were TR (repetition time), 5.42 ms; TE (echo time), 2.42 ms; flip angle, 77°; bandwidth, 399 Hz/Px; slice thickness, 0.70 mm, with interslice gap of 20% and with 64 slices in a single slab; matrix size, 256 × 256. A TE of 2.42 ms was chosen to limit signal loss from magnetic susceptibility effects, and a flip angle of 77° was used to reduce T1 weighting. The acquisition time was 3.30 minutes with the use of two averages. Two-dimensional distortion correction, Prescan normalize, and elliptical filters were applied. The raw data was reviewed on an independent LEONARDO ® workstation, with multiplanar reconstruction performed routinely.

Image Characteristics
Image contrast in CISS is determined by the T2/T1 ratio of the tissue. [2] Tissues with both long T2 relaxation times and short T1 relaxation times have increased signal intensity. Because of high T2/T1 ratio, water and fat have high signal on this sequence. There is excellent contrast between cerebrospinal fluid (CSF) and other structures. The other tissues have poor contrast, and the gray-white differentiation is also not well visualized. Summation of alternating and non-alternating data sets produces an image with homogenous intensity distribution. [1] The advantages of CISS are high signal-to-noise ratio, high contrast-to-noise ratio, [4] and intrinsic insensitivity to motion. [2]

Clinical Applications
Because of the image characteristics described above, CISS sequence plays an important role in evaluating structures surrounded by CSF. It is useful for imaging lesions that are relatively isointense to CSF on T1W and T2W images. [5] Specific applications are described below.

Evaluation of the cranial nerves
Three-dimensional CISS is routinely used in the assessment of cerebellopontine angle lesions, inner ear structures and the internal auditory canal (IAC). [6] With this sequence, the fine structure of the cranial nerves VII and VIII and the membranous labyrinth of the internal ear can be clearly demonstrated. This has facilitated detection of small intracanalicular lesions and diagnosis of the nerve of origin, depending upon the exact location in the IAC. This helps us to precisely diagnose schwannomas arising from the cochlear nerve [ Figure 1]. CISS images can be acquired in any plane but most commonly in the axial plane, for cranial nerve imaging. However, for evaluating the VII-VIII cranial nerve complex, it is helpful to obtain images in the coronal or oblique sagittal plane perpendicular to the IAC or to reconstruct these from the source axial images. [7] CISS is considerably superior to 3D turbo spin-echo (TSE) for nerve visualization in the cerebellopontine angle; and just as good as 3D TSE, in the internal auditory canal. The inclusion of CISS in an MRI imaging protocol of the facial and vestibulocochlear nerves is therefore recommended. [8] Trigeminal neuralgia is caused most commonly by compression of the root entry zone of the trigeminal nerve by a vascular loop. [9] This compression and displacement of the nerve by the vascular loop is well evaluated by the CISS sequence [ Figure 2], which demonstrates the thinning of the root entry zone and allows exact identification of the vascular loop. It has been proposed as the initial screening procedure for all patients with refractory trigeminal neuralgia, especially if surgical intervention is being considered. [10] Contrast-enhanced CISS is useful for evaluating the trigeminal ganglion [11] and the cisternal segment of the nerve.
Orbital masses may arise from optic nerves (e.g., optic glioma) or other nerves in the orbit (e.g., nerve sheath tumor). Both these tumors are known to occur in patients with neurofibromatosis. [12] The CISS sequence can define the relationship of the tumor to the optic nerve and differentiate between these tumors on the basis of the location of the tumor and the thickening and encasement of the optic nerve [ Figure 3].

Evaluation of the cisternal spaces and cavernous sinus
Malignancies and infectious processes like granulomas may spread along the basal cisterns. Granulomas are seen as nodular structures in the cisterns and are related to the cranial nerves. While infectious processes are classically evaluated on contrast-enhanced images, [13] it should be kept in mind that these nodules or basal infiltrates are well depicted on CISS and may sometimes be missed on other sequences if they are isointense to CSF and do not show enhancement [ Figure 4]. sequences and have thin walls. [14] In postoperative cases, CISS may help to differentiate between a recurrent arachnoid cyst and a postoperative cavity by demonstrating adhesions [ Figure 5].

Arachnoid cysts follow CSF signal intensity on all pulse
The imaging findings of Tolosa-Hunt syndrome are classical but may be subtle. [15] MRI may show only slight enlargement or alteration in the shape of the cavernous sinus, but this is well seen on a CISS sequence [ Figure 6].

Diagnosis of neurocysticercosis
Identification of the scolex is essential for making a definitive diagnosis of neurocysticercosis (NCC). This scolex may be missed on routine sequences, but a 3D sequence like CISS will demonstrate it [Figures 7A-C]. We have seen this in several of our patients with NCC and hence have included this sequence in our protocol of MRI for suspected NCC.
While cysts of neurocysticercosis are most often located in the cerebral parenchyma, they may also be found in the ventricles or basal cisterns, or both. Intraventricular cysticercal cysts constitute 7% to 20% of neurocysticercosis infections. [16] Most of these cysts are located in the fourth ventricle. The mortality and morbidity arise from acute obstructive hydrocephalus. As they are surrounded by CSF, which is of the same signal intensity as the cyst fluid, they may be difficult to identify on routine sequences. However, the cyst wall and scolex are well visualized on CISS [ Figure 7D]. The increased sensitivity of the 3D CISS  A 56-year-old male patient presented with headache, neck pain, and fever for 1 month, right hemiparesis for 10 days and altered sensorium for 1 day. Axial T2W (A) and T1W contrast-enhanced (B) images do not show any abnormality in the basal cisterns. Abnormal T2-hyperintense signal is present in the left cerebellar hemisphere (arrow), which showed restricted diffusion (not shown) suggestive of an acute infarct. Axial CISS image (C) shows nodular soft tissue (arrow) in the pre-pontine cistern, which was diagnosed to be a fungal granuloma. Axial CISS image acquired a few sections higher (D) shows a fungal granuloma (arrow) abutting the left trigeminal nerve (arrowhead) Figure 3 (A,B): Orbital neurofibroma. A 3-year-old boy had proptosis since birth and multiple café-au-lait spots. T2W axial image (A) shows a large intraorbital mass (arrow). In addition, multiple areas of increased signal intensity (arrowheads) are seen in the pons and both middle cerebral peduncles (representing "neurofibromatosis bright objects"). CISS image (B) shows normal thickness of the optic nerve (arrow) and of the CSF sheath around it, excluding an optic nerve origin for the tumor. These findings are in keeping with a diagnosis of plexiform neurofibroma rather than optic glioma sequence is due to its higher contrast-to-noise ratio and may also be related to accentuation of the T2 value between the cystic fluid and the surrounding CSF. [17] Evaluation of CSF rhinorrhea A 3D CISS sequence is a reliable noninvasive investigation to evaluate patients with CSF rhinorrhea [ Figure 8]. Also, it does not involve ionizing radiation [18] and thus allows repeated follow-up studies to be performed. However, bony defects are not well visualized.

Evaluation of the ventricular system
Because of high contrast, a 3D CISS sequence is used to study the CSF pathways [19] and lesions impeding CSF flow. It can reveal various causes of obstructive hydrocephalus, such as congenital acqueductal stenosis or membranes; [19] or other intraventricular obstructive lesions, e.g., enlarged Virchow-Robin spaces [ Figure 9].
The 3D CISS sequence can provide additional information    for better definition of other intraventricular lesions as well. Cyst walls -their extent and margins -are clearly depicted on 3D CISS images. [1] Tiny colloid cysts that may be missed on routine sequences are detected on the CISS sequence [ Figure 10].

Evaluation of brain tumors
The visualization of a CSF cleft on CISS sequence allows for the differentiation between intra-and extra-axial tumors. The direction of displacement of the adjacent nerves and vessels gives a clue as to the location of the tumor. Intra-axial tumors will displace these laterally [ Figure 11]. The exact location and extent of the tumor and the presence of intra-tumoral cysts are also well visualized on this sequence. Tumors located in the subarachnoid space are better depicted on this sequence than on other sequences. [20] It can help in better delineation of the borders and extent of intraventricular tumors [ Figure 12].

Giant arachnoid granulations
Filling defects in the dural venous sinuses may be caused by thrombosis, tumors (meningiomas) or large arachnoid granulations. Arachnoid granulations are normal structures that may be mistaken for pathology. [21] These can be diagnosed by the typical imaging characteristics, such as the CSF-signal-intensity pattern on T1W and T2W images. [22] The rent in the dura and the communication with the subarachnoid space, as well as the intrinsic vessels, are clearly seen on CISS sequence [ Figure 13].

Evaluation of diseases of the spine and spinal cord
Spinal vascular malformations may show subtle findings on routine sequences. CISS can clearly demonstrate the engorged pial venous plexus associated with these lesions. The associated cord signal abnormality is better appreciated on a T2 sequence. [5] In cases of spinal trauma, the avulsion of the roots of the brachial plexus is best demonstrated on a CISS sequence. Late complications of trauma, like focal pial adhesions, cord tethering and traumatic syringohydromyelia, are better visualized with CISS than with conventional sequences. [5] Post-myelography adhesions [ Figure 14], with displacement of the cord and globules of retained contrast, can be well demonstrated in arachnoiditis. Similarly, focal displacement of the spinal cord in ventral cord herniation [ Figure 15] is also well visualized on this sequence.
In patients with syringomyelia, CISS sequence can detect subarachnoid webs, cavitations in the syrinx [4] and metameric segmentations in cases of Arnold-Chiari malformation. [5] The flow void artifact is decreased in the  CISS sequence as compared to other T2W sequences. The detection of subarachnoid adhesions by this sequence plays an important role in identifying those patients who require surgical decompression of syringomyelia.

Advantages and limitations
The increased sensitivity of the 3D CISS sequence is an outcome of the accentuation of the T2 values between CSF and pathological structures. [4] The thin contiguous sections and high in-plane resolution make it possible to depict minute structures. Any desired imaging plane can be obtained by the multiplanar reconstructive technique. [1] There is minimal signal loss due to CSF pulsations. The limitation includes long image-acquisition times. [4] Though the inherent lack of tissue characterization is mentioned as a limitation, [5] we have found this sequence to have some role in tissue characterization of intraventricular and extraaxial lesions.

Conclusion
Three-dimensional CISS sequence provides superior topographic information that helps to delineate the exact location of various cranial and spinal pathologies. Often, we have found that this sequence provides information that is not provided by other spin-echo sequences. Apart from the well-recognized applications in the evaluation of cranial nerves, CSF rhinorrhea and aqueduct stenosis, we have found the CISS sequence to be useful in evaluating the cisternal spaces, cavernous sinuses and ventricular system in terms of detecting subtle CSF-intensity lesions that may be missed on routine spin-echo sequences. This information plays an important role in deciding the mode of management of these conditions.