Journal Scan – This Month in Other Journals, June 2017

Elshafeey N, Hassan I, Zinn PO, Colen RR. From K-space to Nucleotide. Top Magn Reson Imaging. 2017;26(1):1. doi:10.1097/RMR.0000000000000114.

Radiogenomics is a relatively new field within radiology that links different imaging features with diverse genomic events. Genomics advances provided by the Cancer Genome Atlas and the Human Genome Project have enabled researchers to harness and integrate this information with noninvasive imaging phenotypes to create a better 3-dimensional understanding of tumor behavior and biology.  This review summarizes the radiogenomic literature regarding brain tumors, both glioblastoma and lower grades.

As you know, the typical gross appearance of glioblastoma on MR is characterized as an irregular, ring-enhancing tumor with a central necrotic core and surrounding area of FLAIR hyperintensity. Each of these 3 imaging components (aka. phenotypes) of the tumor reflect a distinct tumor biology such as neovascularization and active tumor [contrast-enhancing component], edema/invasion (peritumoral T2/FLAIR hyperintensity), or cell death (necrosis). As an example of the potential power of volumetric features of glioblastoma on prognosis, in a cohort of 78 patients glioblastoma tumor volumes were quantified and combined with patient age and Karnofsky performance score (KPS) to create an easy-to-use 3-step scoring system VAK (Volume-Age, KPS) that can predict patient outcome.

Additionally, specific genomic and epigenetic events have shown a predilection for specific locations within the brain. As background, MGMT, a gene that encodes for a DNA repair enzyme, is associated with a better survival in those patients with MGMT promoter methylation receiving alkylating agents such as temozolomide.  In treatment-naive glioblastoma patients, it has been found that patients with unmethylated O-6- methylguanine-DNA methyltransferase (MGMT) promoter predominated in the right temporal lobe. Glioblastoma with MGMT promoter methylation, EGFR amplification, and EGFRvIII mutations tended to occur in in the left temporal lobe.  Most IDH1-mutated and intact PTEN tumors were in the frontal lobe.

3 tables, 4 figures

Wu TY, Yassi N, Shah DG, et al. Simultaneous Multiple Intracerebral Hemorrhages (SMICH). Stroke. 2017;48(3):581-586. doi:10.1161/STROKEAHA.116.015186.

The authors analyzed clinical characteristics and outcome of simultaneous multiple intracerebral hemorrhage patients from 2 comprehensive stroke centers. Baseline imaging from consecutive intracerebral hemorrhage (ICH) patients (n=1552) from Helsinki ICH study and Royal Melbourne Hospital ICH study were screened for simultaneous multiple intracerebral hemorrhage. ICH pathogenesis was classified according to the structural lesion, medication, amyloid angiopathy, systemic/other disease, hypertension, undetermined classification system (SMASH-U). Of 1452 patients, 85 (5.9%) were classified as simultaneous multiple intracerebral hemorrhages. Pathogenesis of simultaneous multiple intracerebral hemorrhages patients was less often hypertensive (20%), more often associated with systemic coagulopathy (12%), and trended toward more cerebral amyloid angiopathy (32%) compared with single intracranial hemorrhage patients. Simultaneous multiple intracerebral hemorrhage was not associated with 90-day mortality. Simultaneous multiple intracerebral hemorrhage has been considered uncommon in ICH but 4 of 6 hospital-based studies in the past decade have reported simultaneous multiple intracerebral hemorrhage presenting in between 4.7% and 5.9% or ≈1 in every 20 of all ICH patients. In 14 (16%) simultaneous multiple intracerebral hemorrhage patients in this study, the secondary hematoma was <5 mm in diameter; therefore, thicker CT slices in the older studies may have affected the ability to define multiple hemorrhages.

So not that uncommon, and look for the underlying pathology. Think hypertensive angiopathy, cerebral amyloid angiopathy, structural vascular abnormalities, medication related, other systemic causes, and undefined causes. Systemic causes include hepatic cirrhosis, systemic coagulopathy, cerebral venous sinus thrombosis, and drug-induced coagulopathy.

Alemseged F, Shah DG, Diomedi M, et al. The Basilar Artery on Computed Tomography Angiography Prognostic Score for Basilar Artery Occlusion. Stroke. 2017;48(3):631-637. doi:10.1161/STROKEAHA.116.015492.

This study aimed to assess the prognostic value of a new radiological score: The Basilar Artery on Computed Tomography Angiography (BATMAN) score. A retrospective analysis of consecutive stroke patients with basilar artery occlusion diagnosed on computed tomographic angiography was performed. BATMAN score is a 10-point CTA–based grading system which incorporates thrombus burden and the presence of collaterals.

This is a ten-point scale, with the basic grades of 2 points for each PCom and 1 point for a hypoplastic PCom (defined as smaller than 1 mm) if in continuity with the top of the basilar artery via a P1 PCA segment, or 3 points for each fetal PCom. 1 point if either intracranial vertebral artery was patent. 1 point for each patent segment of the basilar artery, the proximal segment, extending from the vertebrobasilar junction to the origin of AICAs, the middle segment from the origins of AICAs to the origin of SCAs, and the rostral segment from the origin of SCAs to its rostral end; and 1 point for each patent P1 segment of PCA.

Reliability was assessed with intraclass coefficient correlation.  The derivation cohort included 83 patients with 41 in the validation cohort. In receiver operating characteristic (ROC) analysis, BATMAN score had an area under receiver operating characteristic curve of 0.81.  Interrater agreement was substantial (intraclass coefficient correlation, 0.85). BATMAN score had greater accuracy compared with Posterior Circulation Collateral score. The authors note that patients with unfavorable BATMAN score are less likely to have a good outcome, even when successful recanalization is achieved. The prognostic value of BATMAN score applied to patients treated within and beyond 6 hours. Patients with favorable BATMAN score may achieve good outcomes after recanalization, even in delayed time windows. This emphasizes the importance of collateral assessment in the posterior circulation, analogous to the more established role of collateral assessment in the anterior circulation.

Ben-Abraham EI, Chen J, Felmlee JP, et al. Feasibility of MR elastography of the intervertebral disc. Magn Reson Imaging. 2017;39:132-137. doi:10.1016/j.mri.2015.12.037.

The purpose of this study is to determine if magnetic resonance elastography (MRE) can detect shear wave propagation in the IVD and assessing its stiffness using a clinical MRI scanner, and to compare the experimental results with a finite element model of intervertebral disc MRE. MRE is a sensitive, phase contrast-based imaging technique for non-invasively mapping the mechanical properties of tissues.  Liver MRE has great diagnostic accuracy for hepatic fibrosis, and shows increasing liver stiffness with the stage of fibrosis. A recent study demonstrated MRE in ex vivo human IVDs for measuring the stiffness of the NP at 1250 Hz using a 7 T scanner. That study showed a significant reduction in NP shear modulus with degeneration, which was shown to correlate with T2 relaxation times.

MRE was performed on two ex-vivo baboon lumbar spine motion segments (L3–L4) with the posterior elements removed at a range of frequencies (1000–1500 Hz) using a standard clinical 1.5 T MR scanner. Propagating waves were visualized in an axial cross-section of the baboon IVDs in all three motion-encoding directions, which resembled wave patterns predicted using finite element modeling. The baboon nucleus pulposus showed an average shear stiffness of 79 kPa at 1000 Hz. These results suggest that MRE is capable of visualizing shear wave propagation in the IVD, assessing the stiffness of the nucleus of the IVD.

The authors describe several challenges to using MRE in the intervertebral disc including disc heterogeneity, having a very stiff outer shell (the annulus) and a relatively soft inner core (the nucleus). The IVD is small, and very stiff, at least relative to most tissues assessed using MRE in the literature. To achieve appropriate wave resolution, a very high driving frequency is needed to characterize the disc, similar to work done on hyaline cartilage using MRE at very high frequencies (1–10 kHz).  The nucleus pulposus shows significant viscoelastic effects, and have mechanical properties that are dependent on the loading frequency.

So to summarize, elastography relatively easy in a gigantic organ like the liver which is close to the surface, and really tough for a small deep structure like the disc.

Brooks NP. Central Cord Syndrome. Neurosurg Clin N Am. 2017;28(1):41-47. doi:10.1016/

This is a nice review article on central cord syndrome. Central cord syndrome (CCS) is most commonly caused by blunt trauma. Initially described in the 1950s, its clinical description has changed little since that time. CCS results in weakness of the arms with relative preservation of leg strength. Bladder dysfunction with urinary retention can also be seen in this syndrome. CCS often occurs in elderly patients with underlying cervical stenosis. It also can occur in younger patients and is associated with cervical spine fractures or traumatic disc herniation. Initial proposed mechanism of injury was that mechanical compression of the spinal cord caused injury to the central region of the spinal cord, causing central cord edema and occasionally hematoma formation, leading to the dysfunction of the medial portion of the lateral corticospinal tract. More recent autopsy studies suggest that the injury and axonal breakdown is localized to the white matter of the lateral corticospinal tracts with sparing of the central gray matter, with no hemorrhage. The most consistent finding on MRI is hyperintense signal on gradient T2 echo MRI within the cervical spinal cord and evidence of cord compression. T2 signal (cord edema) correlates with the initial motor score. The treatment of CCS remains controversial. When initially described, surgical intervention was not advocated because the natural history (or conservative treatment) seemed to be better than the surgical treatment. The use of surgery to treat patients with CCS still does not represent the most common treatment modality, but surgical intervention has become more common in the treatment of CCS over the last decade, increasing from 15% to 30%.

2 tables, 1 figure

Holbrook J, Saindane AM. Imaging of Intracranial Pressure Disorders. Neurosurgery. 2017;80(0):341-354. doi:10.1227/NEU.0000000000001362.

This is another very nice review article with multiple figures covering both intracranial hypertension and intracranial hypotension. Although there are multiple hypotheses for the etiology of IIH mainly focused on obesity and metabolic dysfunction, there is no known cause of the development of IIH. IIH occurs most frequently among obese women of childbearing age. Risk factors for development of IIH include high body mass index, recent weight gain, and obstructive sleep apnea.  Transverse sinus stenosis (TSS) is found in a clear majority of patients with IIH; however, it remains debatable whether it is a cause (from venous outflow obstruction) or an effect (from extrinsic compression) of elevated ICP, or both (see last month’s podcast: J Neurosurg. 2017;126(2):347-353. doi:10.3171/2015.12.JNS152033).

Imaging findings in IIH are many and include:

  • Distention of perioptic nerve space
  • Kinked optic nerve, and flattened posterior sclera
  • Concavity of superior margin of pituitary or empty sella
  • Skull-base meningoceles and encephaloceles
  • Lower cerebellar tonsillar position than controls which may have a “peglike” morphology to the tonsils (Chiari 1 like appearance can occur in both IIH and SIH).
  • Relatively low prevalence of “slitlike” ventricles
  • Smooth tapered narrowing of 1 or both distal transverse venous sinuses is almost universally present in IIH (what this means clinically is debatable, as is the utility of looking for this stenosis on MR venography vs. going directly to catheter venography and manometry looking for a pressure gradient).

The cause of SIH is typically a spinal CSF leak. Skull base CSF leaks are unlikely to result in the clinical syndrome of SIH. In addition to postoperative and posttraumatic CSF leaks, CSF leaks in the spine may originate from degenerative changes such as disc herniations and osteophytes, as well as spinal meningeal diverticula.

Imaging findings in SIH include:

  • Enlargement of pituitary
  • Dural thickening / extradural collections
  • Enlarged venous sinuses
  • Brainstem sagging, crowding of basal cisterns
  • Low cerebellar tonsils
  • Spine epidural venous enlargement and extradural collections

Much more to this review, so check it out.

14 figures

Dowdell J, Erwin M, Choma T, Vaccaro A, Iatridis J, Cho SK. Intervertebral Disk Degeneration and Repair. Neurosurgery. 2017;80(3S):S46-S54. doi:10.1093/neuros/nyw078.

This is an excellent and comprehensive review article covering the complex topic of intervertebral disc degeneration and repair. Topics covered include the anatomy and function of the IVD, nutrition of the disc, and normal IVD aging.  Mechanisms of degeneration are covered including genetic and biochemical factors. Therapeutic agents are covered, such as protein injections (growth factors), gene based therapy, cell therapy and tissue engineering.

They conclude that the process of IVD degeneration is complex and multifactorial, and thus the solutions for reversing this process will be equally if not more complex and likely involve multiple solutions depending on the disease phenotype and progression.

Lerch JP, van der Kouwe AJW, Raznahan A, et al. Studying neuroanatomy using MRI. Nat Neurosci. 2017;20(3):314-326. doi:10.1038/nn.4501.

This is an extensive and detailed review of the methods and pitfalls in using advanced imaging techniques for neuroanatomy.

As the authors state: “The ability to obtain high-quality, detailed information from in vivo imaging has clearly revolutionized our understanding of neuroanatomy and structure–function relations and shed insights into multiple disease processes. Yet there are myriads of issues surrounding acquisition, analysis, study design and interpretation that need to be considered. This review provides readers with an overview of these issues to equip them to select the most appropriate toolkit for their needs.”

MR can assess the macroscopic and microscopic aspects of the brain.

There are five domains to studying size and shape at the macro- or mesoscopic scale:

  1. Manual volumetry involves trained anatomists manually segmenting regions of interest from brain scans. While in many ways manual volumetry is still the gold standard, it is hard to scale to multiple scans.
  2. Automatic segmentation algorithms aim to replace manual volumetry for most applications. In some cases manually segmented data sets are used to parcellate new databases on some combination of linear and nonlinear image registration, tissue classification and related image features, while for other algorithms no manual training is necessary.
  3. Two classes of morphometry algorithms are commonly used to analyze neuroanatomy without the prior constraint of defined regions of interest: voxel-based morphometry (VBM) and deformation-based morphometry (DBM). In VBM, the brain is classified into white matter, gray matter and cerebrospinal fluid; a single tissue class is selected, then blurred with a Gaussian kernel to give an estimate of the local amount of that tissue type at every voxel, then compared across subjects.  In DBM, brains are nonlinearly deformed toward a common space or each other, and deformation fields are either directly analyzed or reduced to a scalar measure of volume change, the Jacobian determinant, before comparisons across scans.
  4. The complex folding pattern of the cerebral cortex challenges computational neuroanatomy, but this has improved with the development of surface-based algorithms where the inside and outside surfaces of the cortex are segmented using deformable models, and measures such as cortical thickness and surface area are extracted.
  5. White-matter tract locations and sizes can be estimated using diffusion tractography.

The study of microstructure, which in MRI refers to the distribution of the contents of a voxel, has been primarily the domain of diffusion MRI. Here the thermally-driven, random motion of water molecules is a probe of the local microenvironment, and the restriction of that motion is used to infer the organization of the tissue inside the imaging voxel.

Impossible to summarize accurately the scope of this paper, so I won’t.  But please read this if your area of research is advanced imaging such as DTI or VBM.

6 figures

Journal Scan – This Month in Other Journals, June 2017
Jeffrey Ross • Mayo Clinic, Phoenix

Dr. Jeffrey S. Ross is a Professor of Radiology at the Mayo Clinic College of Medicine, and practices neuroradiology at the Mayo Clinic in Phoenix, Arizona. His publications include over 100 peer-reviewed articles, nearly 60 non-refereed articles, 33 book chapters, and 10 books. He was an AJNR Senior Editor from 2006-2015, is a member of the editorial board for 3 other journals, and a manuscript reviewer for 10 journals. He became Editor-in-Chief of the AJNR in July 2015. He received the Gold Medal Award from the ASSR in 2013.