MAGNETIC RESONANCE IMAGING CHARACTERISTICS IN FOUR DOGS WITH CENTRAL NERVOUS SYSTEM NEOSPOROSIS

Neosporosis is a polysystemic disease that can affect dogs of any age and can cause inflammation of the central nervous system. Antemortem diagnosis can be challenging, as clinical and conventional laboratory test findings are often nonspecific. A previous report described cerebellar lesions in brain MRI studies of seven dogs and proposed that these may be characteristic for central nervous system Neosporosis. The purpose of this retrospective study was to describe MRI characteristics in another group of dogs with confirmed central nervous system neosporosis and compare them with the previous report. The hospital's database was searched for dogs with confirmed central nervous system neosporosis and four observers recorded findings from each dog's MRI studies. A total of four dogs met inclusion criteria. Neurologic examination was indicative of a forebrain and cerebellar lesion in dog 2 and multifocal central nervous system disease in dogs 1, 3, and 4. Magnetic resonance imaging showed mild bilateral and symmetrical cerebellar atrophy in three of four dogs (dogs 2, 3, 4), intramedullary spinal cord changes in two dogs (dogs 3, 4) and a mesencephalic and metencephalic lesion in one dog (dog 2). Multifocal brain lesions were recognized in two dogs (dogs 1, 4) and were present in the thalamus, lentiform nucleus, centrum semiovale, internal capsule, brainstem and cortical gray matter of the frontal, parietal or temporal lobe. Findings indicated that central nervous system neosporosis may be characterized by multifocal MRI lesions as well as cerebellar involvement in dogs.     

LOW-AND HIGH-FIELD STRENGTH MAGNETIC RESONANCE IMAGING TO EVALUATE THE BRAIN IN ONE NORMAL DOG AND TWO DOGS WITH CENTRAL NERVOUS SYSTEM DISEASE

The brain of one control dog and two dogs with spontaneous central nervous system pathology (one hydrocephalus, one meningoencepholocoele) were examined with low- and high-field-strength magnetic resonance devices to evalute the suitability of low-field magnets for canine brain imaging. We used 0.1 T and 1.0 T magnetic resonance (MR) imagers. The best image quality was seen 1.0 T imaging due to better signal-to-noise-ratio, but both systems produced satisfactory anatomic images of the brain.     

MAGNETIC RESONANCE IMAGING FEATURES AND OUTCOME FOR SOLITARY CENTRAL NERVOUS SYSTEM COCCIDIOIDES GRANULOMAS IN 11 DOGS AND CATS

Little published information is available to guide therapy for canine and feline patients with Coccidioides infections involving the central nervous system (CNS). The purpose of this cross‐sectional retrospective study was to describe magnetic resonance imaging (MRI) features and outcome for a group of dogs and cats with solitary CNS Coccidiodes granulomas. Nine canine and two feline cases met inclusion criteria; four diagnosed and treated with surgery and fluconazole and seven diagnosed by serology or cytology and treated medically. Three cases had left Coccidioides endemic areas long before developing neurological disease. The MRI lesions shared many features with neoplastic masses. The extra‐axial granulomas often had a lack of a distinct border between the mass and neural parenchyma. Four cases were extra‐axial and seven were intra‐axial, but distinguishing between extra‐axial and intra‐axial locations was sometimes challenging. The surgical cases had good outcomes and histology allowed definitive diagnosis. Medically managed patients also had generally good outcomes, with resolution of clinical signs in most cases. Findings indicated that distinction between neoplasia and focal Coccidioides granulomas based on MRI features is likely to be imprecise. Demonstration of the organism by cytology or histology is required for definitive diagnosis. The role of surgery for improving the outcome of brain or spinal coccidioidomycosis granulomas warrants further study.     

MAGNETIC RESONANCE IMAGING OF SPONGY DEGENERATION OF THE CENTRAL NERVOUS SYSTEM IN A LABRADOR RETRIEVER

A 7-month-old, neutered female Labrador Retriever was evaluated for tetraparesis and subtle cerebellar dysfunction. Clinical signs progressed over a period of 6 weeks to severe ataxia, hypermetria, intention tremors, and finally non-ambulatory tetraparesis. On magnetic resonance imaging of the brain there were large, bilaterally symmetrical, ovoid lesions in the region of the deep cerebellar nuclei that were hyperintense on T2-weighted and proton density images and hypointense on T1-weighted images. There were similar but smaller bilaterally symmetrical lesions present within the thalamus. Euthanasia was performed and lesions consistent with the previously described spongy degeneration of Labrador Retrievers were identified. This disease and its relation to similar human heritable leukodystrophies are discussed.     

LOW FIELD MAGNETIC RESONANCE IMAGING OF THE CANINE CENTRAL NERVOUS SYSTEM

Magnetic resonance (MR) imaging is a relatively new method of medical imaging. MR studies on the normal canine central nervous system were performed using a low field MR scanner. The regions of interest were the head, neck, and lumbar region. The MR findings in two patients with brain atrophy and cervical neck disc protrusion were also evaluated. Based on our findings it appears that low-field scanners will be satisfactory for use in veterinary diagnostic imaging.     

EARLY POSTOPERATIVE MAGNETIC RESONANCE IMAGING FINDINGS IN FIVE DOGS WITH CONFIRMED AND SUSPECTED BRAIN TUMORS

Early postoperative neuroimaging has been performed in people for over 20 years to detect residual brain tumor tissue and surgical complications. The purpose of this retrospective study was to describe characteristics observed using early postoperative magnetic resonance imaging in a group of dogs undergoing craniotomy for brain tumor removal. Two independent observers came to a consensus opinion for presence/absence of the following MRI characteristics: residual tumor tissue; hemorrhage and ischemic lesions; abnormal enhancement (including the margins of the resection cavity, choroid plexus, meninges) and signal intensity changes on diffusion‐weighted imaging. Five dogs were included in the study, having had preoperative and early postoperative MRI acquired within four days after surgery. The most commonly observed characteristics were abnormal meningeal enhancement, linear enhancement at margins of the resection cavity, hemorrhage, and a thin rim of hyperintensity surrounding the resection cavity on diffusion‐weighted imaging. Residual tumor tissue was detected in one case of an enhancing tumor and in one case of a tumor containing areas of hemorrhage preoperatively. Residual tumor tissue was suspected but could not be confirmed when tumors were nonenhancing. Findings supported the use of early postoperative MRI as a method for detecting residual brain tumor tissue in dogs.     

MAGNETIC RESONANCE IMAGING FEATURES OF ORBITAL INFLAMMATION WITH INTRACRANIAL EXTENSION IN FOUR DOGS

This retrospective study describes the clinical and magnetic resonance (MR) imaging features of chronic orbital inflammation with intracranial extension in four dogs (two Dachshunds, one Labrador, one Swiss Mountain). Intracranial extension was observed through the optic canal (n=1), the orbital fissure (n=4), and the alar canal (n=1). On T1-weighted images structures within the affected skull foramina could not be clearly differentiated, but were all collectively isointense to hypointense compared with the contralateral, unaffected side, or compared with gray matter. On T2-, short tau inversion recovery (STIR)-, or fluid-attenuated inversion recovery (FLAIR)-weighted images structures within the affected skull foramina appeared hyperintense compared with gray matter, and extended with increased signal into the rostral cranial fossa (n=1) and middle cranial fossa (n=4). Contrast enhancement at the level of the affected skul foramina as well as at the skull base in continuity with the orbital fissure was observed in all patients. Brain edema or definite meningeal enhancement could not be observed, but a close anatomic relationship of the abnormal tissue to the cavernous sinus was seen in two patients. Diagnosis was confirmed in three dogs (one cytology, two biopsy, one necropsy) and was presumptive in one based on clinical improvement after treatment. This study is limited by its small sample size, but provides evidence for a potential risk of intracranial extension of chronic orbital inflammation. This condition can be identified best by abnormal signal increase at the orbital fissure on transverse T2-weighted images, on dorsal STIR images, or on postcontrast transverse or dorsal images.     

MAGNETIC RESONANCE IMAGING FINDINGS IN THE SPINE OF SIX DOGS DIAGNOSED WITH LYMPHOMA

Lymphoma is one of the most common neoplasms in the dog. Despite its prevalence and the increasing use of advanced diagnostic imaging in veterinary patients only few reports of magnetic resonance imaging (MRI) findings in spinal lymphoma have been published to date. The purpose of this retrospective case series study was to describe the MRI findings in dogs with confirmed lymphoma affecting the spine and/or paraspinal soft tissues. Medical records were searched for patients that had MRI of the spine and a diagnosis of lymphoma during the period of 2005–2015. Data recorded from retrieved MRI studies were presence of focal or multifocal disease, structures involved, and signal characteristics on T2‐W, short tau inversion recovery (STIR), and T1‐W sequences prior to and following intravenous contrast medium administration. Six dogs met the inclusion criteria. Common findings included multifocal disease (4/6), vertebral involvement (5/6), spinal cord compression (4/6), and involvement of more than one spinal compartment (medullary cavity, vertebral canal, paraspinal soft tissues) (6/6). Vertebral changes were confined to the medullary cavity without evidence of cortical osteolysis. There was questionable involvement of the spinal cord in one case. All spinal and paraspinal lesions identified were T2‐W isointense to hyperintense, STIR hyperintense, T1‐W hypointense to isointense, and showed variable moderate to strong contrast enhancement. Additional lesions identified were enlarged intraabdominal lymph nodes, hepatomegaly, splenomegaly, and a splenic nodule. The STIR and T1‐W postcontrast sequences were subjectively the most useful in identification of the spinal and paraspinal lesions.     

CLINICAL AND MAGNETIC RESONANCE IMAGING FEATURES OF IDIOPATHIC OCULOMOTOR NEUROPATHY IN 14 DOGS

Ophthalmoplegia/ophthalmoparesis (internal, external, or both) has been reported in dogs secondary to neoplasia affecting the oculomotor nerve and is usually given a poor prognosis. The purpose of this retrospective study was to describe the clinical findings, magnetic resonance imaging (MRI) findings, management, outcome, and follow‐up in a group of canine cases with idiopathic oculomotor neuropathy. Inclusion criteria included cases with ophthalmoplegia/ophthalmoparesis (internal, external or both) as sole neuroophthalmologic signs, complete ophthalmic and neurologic examination, head MRI, and a minimum follow‐up period of 1 year. Dogs with progressive neurological signs not related to oculomotor neuropathy were excluded. Fourteen cases met the inclusion criteria. All cases were unilaterally affected. Magnetic resonance imaging showed equivocal enlargement of the oculomotor nerve in three cases, mild enlargement in five, and marked enlargement in six. Contrast enhancement was present in 12 cases, being marked in six. When present, the contrast enhancement was focal in eight cases and diffuse in four. The median follow‐up time was 25 months. External ophthalmoparesis improved in seven cases, five cases under no treatment and two under systemic corticosteroid therapy. The clinical signs in the other seven cases remained unchanged. Idiopathic oculomotor neuropathy should be included as a differential diagnosis in dogs presenting with unilateral ophthalmoplegia/ophthalmoparesis (internal, external, or both) with the absence of other neurologic and ophthalmic signs, and with the MRI findings restricted to the oculomotor nerve. Idiopathic oculomotor neuropathy has a good prognosis as the clinical signs do not deteriorate and they can improve without treatment.     

MAGNETIC RESONANCE IMAGING OF ACQUIRED TRIGEMINAL NERVE DISORDERS IN SIX DOGS

The medical records and magnetic resonance (MR) images of dogs with an acquired trigeminal nerve disorder were reviewed retrospectively. Trigeminal nerve dysfunction was present in six dogs with histologic confirmation of etiology. A histopathologic diagnosis of neuritis (n=2) or nerve sheath tumor (n=4) was made. Dogs with trigeminal neuritis had diffuse enlargement of the nerve without a mass lesion. These nerves were isointense to brain parenchyma on T1-weighted (T1W) precontrast images and proton-density-weighted (PDW) images and either isointense or hyperintense on T2-weighted (T2W) images. Dogs with a nerve sheath tumor had a solitary or lobulated mass with displacement of adjacent neuropil. Nerve sheath tumors were isointense to the brain parenchyma on T1W, T2W, and PDW images. All trigeminal nerve lesions enhanced following contrast medium administration. Atrophy of the temporalis and masseter muscles, with a characteristic increase in signal intensity on T1W images, were present in all dogs.     

MAGNETIC RESONANCE IMAGING APPEARANCE OF SUSPECTED ISCHEMIC MYELOPATHY IN DOGS

Ischemia and infarction of the spinal cord is a known cause of acute spinal injury in dogs. Currently, the diagnosis of spinal cord infarction in small animals is based on history, clinical signs, and the exclusion of other differentials with radiography and myelography. It is a diagnosis only confirmed through necropsy examination of the spinal cord. The aim of this paper is to describe the Magnetic resonance imaging (MRI) findings of the spinal cord of dogs with suspected spinal cord infarcts to utilize this technology for antemortem support of this diagnosis. This retrospective study evaluated the spinal MR examinations of 11 dogs with acute onset of asymmetric nonpainful myelopathies. All patients except one (imaged at 2 months) were imaged within 1 week of clinical signs and managed conservatively with minimal medical and no surgical intervention. They were followed clinically for a minimum of 4 months after discharge. MR findings in all dogs were characterized by focal, intramedullary, hyperintense lesions on T2-weighted images with variable contrast enhancement similar to what is reported in humans. Though it could not be used to diagnose spinal cord infarction definitively, MRI was useful in excluding extramedullary spinal lesions and supporting intramedullary infarction as a cause of the acute neurologic signs. Together with the history and clinical examination findings, MRI is supportive of a diagnosis of spinal cord infarction.     

COMPARISON OF FAST SPIN-ECHO AND CONVENTIONAL SPIN-ECHO MAGNETIC RESONANCE SPINAL IMAGING TECHNIQUES IN FOUR NORMAL DOGS

Various magnetic resonance (MR) imaging techniques have been used to assess lumbar spinal abnormalities in people. Four, young adult, clinically normal dogs were used to compare images of the spinal cord acquired using conventional spin-echo and rapid acquisition relaxation-enhanced (RARE), commonly called fast spin-echo (FSE), magnetic resonance imaging techniques. Lateral myelograms were made as an anatomic control. The T2-weighted FSE technique was characterized by better image quality than the T2-weighted conventional spin-echo technique. The short acquisition time with the FSE technique allowed increases in the matrix size and number of excitations, thus improving resolution and signal-to-noise ratio. In canine lumbar spinal MR imaging, use of a FSE technique is recommended to reduce the overall time for imaging and to improve image quality.     

MAGNETIC RESONANCE IMAGING IN THE DIAGNOSIS OF FOCAL GRANULOMATOUS MENINGOENCEPHALITIS IN TWO DOGS

Two dogs with neurologic signs were evaluated by magnetic resonance imaging of the brain. Focal space-occupying lesions were present in both dogs. In the first, the lesion was in the brain stem and in the second, in the cerebellum. In one dog the lesion was only evident after administration of gadolinium-DTPA-dimeglumine. Based on the magnetic resonance images, neoplasia was suspected in both dogs but histopathologically, granulomatous meningoencephalomyelitis was diagnosed.     

MAGNETIC RESONANCE IMAGING FEATURES OF DISCOSPONDYLITIS IN DOGS

The diagnosis of discospondylitis is based mainly on diagnostic imaging and laboratory results. Herein, we describe the magnetic resonance imaging (MRI) findings in 13 dogs with confirmed discospondylitis. In total there were 17 sites of discospondylitis. Eleven (81.1%) of the dogs had spinal pain for >3 weeks and a variable degree of neurologic signs. Two dogs had spinal pain and ataxia for 4 days. Radiographs were available in nine of the dogs. In MR images there was always involvement of two adjacent vertebral endplates and the associated disk. The involved endplates and adjacent marrow were T1‐hypointense with hyperintensity in short tau inversion recovery (STIR) images in all dogs, and all dogs also had contrast enhancement of endplates and paravertebral tissues. The intervertebral disks were hyperintense in T2W and STIR images and characterized by contrast enhancement in 15 sites (88.2%). Endplate erosion was present in 15 sites (88.2%) and was associated with T2‐hypointense bone marrow adjacent to it. In two sites (11.8%) endplate erosion was not MR images or radiographically. The vertebral bone marrow in these sites was T2‐hyperintense. Epidural extension was conspicuous in postcontrast images at 15 sites (88.2%). Spinal cord compression was present at 15 sites (88.2%), and all affected dogs had neurologic signs. Subluxation was present in two sites (11.8%). MRI shows characteristic features of discospondylitis, and it allows the recognition of the exact location and extension (to the epidural space and paravertebral soft tissues) of the infection. Furthermore, MRI increases lesion conspicuity in early discospondylitis that may not be visualized by radiography.     

REVERSIBLE MAGNETIC RESONANCE IMAGING ABNORMALITIES IN DOGS FOLLOWING SEIZURES

Reversible magnetic resonance (MR) imaging lesions have been described in humans following seizures. This condition has not yet been reported in animals. This paper describes reversible abnormalities identified in 3 dogs using MR imaging that was performed initially within 14 days of the last seizure and follow-up imaging that was performed after 10 to 16 weeks of anticonvulsant therapy. All three dogs had lesions in the piriform/temporal lobes, characterized by varying degrees of hyperintensity on T2-weighted images and hypointensity on T1-weighted images. In one dog, contrast enhancement was evident. On reevaluation, partial resolution occurred in all 3 dogs. In a fourth animal with an olfactory meningioma, similar appearing lesions in the temporal cortex and right and left piriform lobes were identified after seizure activity. A surgical biopsy of the temporal cortex and hippocampus was performed and edema, neovascularization, reactive astrocytosis, and acute neuronal necrosis were evident. These histologic findings are similar to those reported in humans with seizures. Recognizing the potential occurrence of reversible abnormalities in MR images is important in developing a diagnostic and therapeutic plan in canine patients with seizures. Repeat imaging after seizure control may help differentiate between seizure-induced changes and primary multifocal parenchymal abnormalities.     

DEVELOPMENT OF A WHOLE BODY MAGNETIC RESONANCE IMAGING PROTOCOL IN NORMAL DOGS AND CANINE CANCER PATIENTS

Whole body magnetic resonance imaging (whole body MR imaging) could potentially provide accurate cancer staging as a single imaging modality. This study was done to develop a whole body MR imaging protocol for a 1.5T MR instrument using four normal Beagle dogs (Phase 1) and then to assess the protocol's feasibility in cancer-bearing dogs (Phase II). In Phase I, anesthetized dogs were placed in dorsal recumbency with limbs flexed along the torso. T1, T2, and short tau inversion recovery sequences were acquired by spin echo or fast spin echo, and also using the more rapid single shot fast spin echo and gradient echo pulse sequences. Three large overlapping fields of view (FOV) were used to visualize the entire body and the sagittal and dorsal imaging planes were compared. Relative examination time, image quality, organ visibility and signal intensity were evaluated. Phase I results were used to establish a protocol that balanced image quality with examination time. In Phase II, whole body MR imaging was done on 10 dogs with cancer. Examination times were 60-75 min. Image quality was sufficient for all known lesions to be visualized, including mass lesions, pulmonary infiltrate, and lymphadenomegaly. Skeletal detail was sufficient to visualize known neoplastic lesions of the appendicular skeleton, yet it was suboptimal because of the large FOV and use of the body coil. Additional modifications of a whole body MR imaging protocol and continued technological improvements in MR imaging will further increase its potential for veterinary cancer staging.     

MAGNETIC RESONANCE IMAGING FEATURES OF INTRACRANIAL ASTROCYTOMAS AND OLIGODENDROGLIOMAS IN DOGS

Astrocytomas and oligodendrogliomas represent one third of histologically confirmed canine brain tumors. Our purpose was to describe the magnetic resonance (MR) imaging features of histologically confirmed canine intracranial astrocytomas and oligodendrogliomas and to examine for MR features that differentiate these tumor types. Thirty animals with confirmed astrocytoma (14) or oligodendroglioma (16) were studied. All oligodendrogliomas and 12 astrocytomas were located in the cerebrum or thalamus, with the remainder of astrocytomas in the cerebellum or caudal brainstem. Most (27/30) tumors were associated with both gray and white matter. The signal characteristics of both tumor types were hypointense on T1‐weighted images (12 each) and hyperintense on T2‐weighted images (11/14 astrocytomas, 12/16 oligodendrogliomas). For astrocytomas and oligodendrogliomas, respectively, common findings were contrast enhancement (10/13, 11/15), ring‐like contrast enhancement (6/10, 9/11), cystic regions within the mass (7/14, 12/16), and hemorrhage (4/14, 6/16). Oligodendrogliomas were significantly more likely to contact the brain surface (meninges) than astrocytomas (14/16, 7/14, respectively, P=0.046). Contact with the lateral ventricle was the most common finding, occurring in 13/14 astrocytomas and 14/16 oligodendrogliomas. No MR features were identified that reliably distinguished between these two tumor types. Contrast enhancement was more common in high‐grade tumors (III or IV) than low‐grade tumors (II, P=0.008).     

NORMAL CANINE BRAIN MATURATION AT MAGNETIC RESONANCE IMAGING

The normal neonatal canine brain exhibits marked differences from that of the mature brain. With development into adulthood, there is a decrease in relative water content and progressive myelination; these changes are observable with magnetic resonance imaging (MRI) and are characterized by a repeatable and predictable time course. We characterized these developmental changes on common MRI sequences and identified clinically useful milestones of transition. To accomplish this, 17 normal dogs underwent MRI of the brain at various times after birth from 1 to 36 weeks. Sequences acquired were T1‐weighted (T1W), T2‐weighted (T2W), fluid attenuated inversion recovery, short tau inversion recovery, and diffusion weighted imaging sequences. The images were assessed subjectively for gray and white matter relative signal intensity and results correlated with histologic findings. The development of the neonatal canine brain follows a pattern that qualitatively matches that observed in humans, and which can be characterized adequately on T1W and T2W images. At birth, the relative gray matter to white matter signal intensity of the cortex is reversed from that of the adult with an isointense transition at 3–4 weeks on T1W and 4–8 weeks on T2W images. This is followed by the expected mature gray matter to white matter relative intensity that undergoes continued development to a mostly adult appearance by 16 weeks. On the fluid attenuated inversion recovery sequence, the cortical gray and white matter exhibit an additional signal intensity reversal during the juvenile period that is due to the initial high relative water content at the subcortical white matter, with its marked T1 relaxation effect.     

MAGNETIC RESONANCE IMAGING FINDINGS IN SMALL RUMINANTS WITH BRAIN DISEASE

Brain disease is an important cause of neurologic deficits in small ruminants, however few MRI features have been described. The aim of this retrospective, case series study was to describe MRI characteristics in a group of small ruminants with confirmed brain disease. A total of nine small ruminants (six sheep and three goats) met inclusion criteria. All had neurologic disorders localized to the brain and histopathologic confirmation. In animals with toxic‐metabolic diseases, there were bilaterally symmetric MRI lesions affecting either the gray matter (one animal with polioencephalomalacia) or the white matter (two animals with enterotoxemia). In animals with suppurative inflammation, asymmetric focal brainstem lesions were present (two animals with listeric encephalitis), or lesions typical of an intra‐axial (one animal) or dural abscess (one animal), respectively. No MRI lesions were detected in one animal with suspected viral cerebellitis and one animal with parasitic migration tracts. No neoplastic or vascular lesions were identified in this case series. Findings from the current study supported the use of MRI for diagnosing brain diseases in small ruminants.     

MAGNETIC RESONANCE IMAGING OF SUBARTICULAR BONE MARROW LESIONS IN DOGS WITH STIFLE LAMENESS

A bone bruise is a magnetic resonance (MR) imaging sign thought to signify acute traumatic microfracture of trabecular bone with hemorrhage and edema in the marrow that may occur without grossly visible disruption of the adjacent cortices or overlying cartilage. In approximately 75% of people with acute anterior-cruciate ligament tears, bone bruises are detected in characteristic locations within the femur and tibia and are best seen as high-signal lesions using fat-suppression sequences. We questioned whether this is a component of naturally acquired stifle lameness in dogs and obtained short-tau inversion recovery (STIR) images of six dogs with stifle lameness. High-signal STIR lesions were detected in five of six (83%) dogs and eight of 12 (67%) limbs. We observed these lesions deep to the intercondylar fossa of the femur and intercondylar eminence of the tibia, which are atypical locations in people. High-signal STIR lesions were detected in dogs with only synovitis, partial tear of the cranial cruciate ligament (CCL) and complete tear of the CCL. One of these lesions was seen in the lateral tibial condyle, a typical location in humans with acute anterior cruciate ligament tear. As the MR imaging appearance of stress fractures and bone bruises are similar, and the high-signal STIR lesions are at attachment sites of the CCL, this finding may be due to stress disease or other unknown causes, rather than bone bruising. High-signal STIR lesions may be a common sign in naturally acquired canine stifle disease, but the pathogenesis, prognostic and diagnostic values need further investigation.