3.1 Epidemiological studies.
HIV is a neurotropic virus, and the central nervous system is vulnerable to it. It was found that more than 90%of AIDS patients pathological changes in neurological systemafter autopsies, which may involvethe brain, spinal cord, peripheral nerves and muscles.Additionally, 11% of AIDS patients are complicated with central nervous system diseases, and 15% have central nervous system lymphoma (ARL-CNS). After HIV infection, the incidence of ARL-CNS rate is as high as 4-10%.Among these patients, the incidence of non-Hodgkin lymphoma(NHL) is significantly higher than that of Hodgkin lymphoma(HL). The prognosis of ARL-CNS is poor,with amedian clinical remission time of 4.2 months and a median survival time after clinical symptom relief of 1.6months.Targeted treatment can improve prognosis, so early diagnosis is very important.
3.2 Diagnosis and Differential Diagnosis of ARL-CNS and Intracranial Infection.
The number of CSF cells in patients with ARL-CNS usually increased only slightly, with an increase in protein, and sugar and chlorine levels within the normal range. These signs overlap with those of AIDS complicated with intracranial infectious diseases.Clinical manifestations of ARL-CNS are also not specific, leading to difficulties in diagnosis. ARL-CNS and infectious diseases present as multiple lesions in conventional MR. It is also very difficult to differentiate two diseases by radiology, which primarily manifested annular or nodular enhancement of MR[1, 9-12].
3.2.1 Conventional MR in Diagnosis and Differential Diagnosis of ARL-CNS.
ARL-CNS usually shows multiple lesions by conventional MR. The lesions are typically located slightly more supratentorial than subtentorial. They can also be located around the ventricle, beside the midline, or under the cortex. The current study shows that lesions involving the paraventricle are statistically significant. Those involving the corpus callosum are even more suggestive of an ARL-CNS diagnosis. ARL-CNS can easily invade the ependyma, pia mater and dura mater and can spread along it, which is similar to the findings of Kasamon. The pvalue involving the ependyma was 0.057, buta larger sample size was required to clarify whether there is a difference between two groups. Most ARL-CNS originates in the perivascular space and shows multicentric infiltrative growth to the periphery, forming a typical "cuff-like" pattern. Tumor mass effect is relatively light, while e peritumoral edema can be light or heavy. Normally, the signals of T1WI and T2WI have no specificity. Masses without necrosis tend to be isointense relative to the grey matter. Hemorrhage is common in ARL-CNS, which is considered to be an inhomogeneous high signal in T1WI.
Toxoplasmosis infection is one of the most common intracranial opportunistic infections in AIDS. The serum toxoplasma IgG test is often either a false negative or false-positive result. The clinical diagnosis is more difficult when the experimental therapeutic effect is poor. Toxoplasma gondii circulated through the blood to the brain, mainly at the junction area of the grey matter and white matter. The supratentorial/subtentorial region can be involved, but rarely the ventricles, ependyma and meninges. MR typically presents multiple intracranial annular enhancement foci, which often involve the basal ganglia. In typical cases,T2WI and enhanced scanning show "target signs", but the incidence is less than 30%. T2WI can show hypointensity, which is associatedto coagulative necrosis. Edema around the focus is severe.After 2-4 weeks of anti-Toxoplasma gondii treatment, the lesion is absorbed or reduced, and the edema effect is reduced. Effective experimental treatment can prompt a diagnosis. After treatment, the area is prone to bleeding easily and shows a high signal on T1WI, which increases the diagnostic difficulty of ARL-CNS.
AIDS complicated with cerebral tuberculosis:In AIDS patients, the incidence of cerebral tuberculosis is second only to pulmonary tuberculosis and lymphoid tuberculosis. The MR showed multiple dot or ring-enhanced lesions at the junction of gray and white matter. Meninges were easily involved, often with hydrocephalus. The annular enhanced wall of tuberculoma is more tensional than that of toxoplasmosis.
PML: PML is different from circular or nodular enhancement lesions such as ARL-CNS, toxoplasmosis and tuberculoma. Here, we are discussing PML because there were four cases in the infection group. PML is an opportunistic demyelination of the central nervous system caused by JC virus infection. PML typical presents as bilateral multiple and asymmetrical white matter lesions. These lesions can involve any part of the supratentorial and infratentorial white matter. Bilateral cerebral hemispheres are often involved, the parietal lobe being the most severely affected, followed by the frontal lobe.Supratentorial leukoencephalopathy is most commonly associated with arcuate fibers(U-shapedfibers). The infratentorial involvement mainly affects the bridge arm, adjacent pons and cerebellum. The lesions have a low signal on T1WI and a high signal on T2WI. Typical lesions are "finger-shaped" and "scallop-shaped". In the current study, enhancement or mild peripheral enhancement were not observed in the lesions upon enhanced scanning.
Another opportunistic infection such as cryptococcus, which causes meningoencephalitis. Typical MR manifestations include thickening and enhancement of the frontal and parietal meninges and formation of a colloidal pseudocyst in the perivascular space of the basal ganglia. Clinically, a clear diagnosis can be obtained from cerebrospinal fluid positive for cryptococcus antigen or positive by ink staining. This condition is more easily distinguished from the above diseases and will not be further discussed here.
3.2. 2 Multimodal MR Differential Diagnosis.
DWI: Lymphoma without necrosis showed high DWI signal and a decreased ADC value, which indicated that diffusion was limited. The differences in ADC values of the ARL-CNS and infection groups were statistically significant. This finding is consistent with the study by Camacho, which showed that a high DWI signal and a decreased ADC value suggested ARL-CNS from toxoplasmosis. The limited diffusion of the solid portion may be due to the tumor cell structure with less cytoplasm, larger nuclei, more euchromatin, a lack of organelles, an abundance of ribosomes, a high nuclear-cytoplasmic ratio, a low water content, rich reticular fibers and other pathological characteristics. The main component of reticular fibers is collagen, which contains little water content. These pathological characteristics lead to the limited diffusion of water molecules in the tumor body and high DWI signal. In our group, seven cases of infectious lesions were hyperintense on DWI, but their ADC values were also hyperintense, indicating that the diffusion was not limited. The cause of DWI hyperintensity was the T2 penetration effect, suggesting that ADC value shouldbeattachedimportancein clinical work. The ADC value excludes the influence of the T2 penetration effect on DWI signals and makes the interpretation of diffusion-weighted imaging more reasonable.
SWI is an imaging sequence based on differences in magnetic sensitivity and the blood oxygen level-dependent (BOLD) effect between tissues. SWI can sensitively display paramagnetic substances in tissues and has significant advantages in displaying microvascular structures and microhemorrhage foci. Hemorrhage and necrosis often occur in ARL-CNS and present as uneven, slightly high signal on T1WI and as multiple punctate/linear and patchy low signal on SWI. Refer to Park for the classification of low SWI signal. The ITSS in ARL-CNS was statistically significantly higher (2-3 times) than in the infection group. There were 3 cases of toxoplasmosis in the infection group, one of which had internal hemorrhage after treatment. ITSS was divided into 3 grades, and the other 2 cases had ITSS grades of 0-1. The other infectious lesions, such as abscesses, tuberculoma, PML, and others, all had ITSS grades of 0-1. These findings are in accordance with those of Lai. The combination of SWI and DWI plays an important role in differentiating brain tumors from infectious diseases.
The MR arterial spin labelling technique (ASL) technique uses water in arterial blood as an endogenous contrast agent by detecting magnetically labelled blood quality. When there is subcurrent passing through the region of interest, the change of tissue signal intensity reflects information of local tissues blood perfusion. With the continuous updates of technology, software and hardware, this technique is now in clinical practice.3D-pCASL is widely used as a safe and reliable method to quantitatively evaluate tumor blood perfusion. Although brain lymphoma may invade vascular endothelial cells and even vascular walls, we found no obvious neovascularization, ASL hypoperfusion was apparent. Da Rocha stated that hypoperfusion was a particular sign of lymphoma that was related to the lack of angiogenesis in tumor tissues and the extrusion and infiltration of microcirculatory vessels by tumor cells. Of the nine ARL-CNS cases, six showed hypoperfusion, a finding similar to that in previous studies of normal immune lymphoma. Among the ten cases of infectious disease, there were two cases of PML with high perfusion in the periphery, and the other eight cases showed low perfusion. There was no significant difference between two groups.
3.2.3 Improvement of diagnosis efficiency in multimodal MR combined with conventional MR
ARL-CNS and infectious lesions often present as multiple lesions on the conventional sequence.They can show supratentorial/subtentorial, subcortical, and/or periventricular, and the ependyma and meninges can be affected. Enhancement methods can be nodular or annular, causing difficulties in differential diagnosis. When the corpus callosum is involved, it is considered ARL-CNS. Infectious lesions such as PML can be considered when the lesions are not enhanced. However, the incidence is relatively low. It is difficult to diagnose ARL-CNS by conventional MR, with a sensitivity of 88.9%, a specificity of 70.0%, and an accuracy of 78.9%.Conventional MR combined with DWI/ADC has improved sensitivity, but its specificity is decreased and its accuracy is unchanged. DWI, as a more commonly used clinical sequence, has the advantages of a short time and insensitivity to motion artifacts. Additional DWI sequence scans can reduce the missed diagnosis rate of ARL-CNS. For AIDS patients, the nature of intracranial lesions is more complex. We recommend DWI sequence scanning to assess the possibility of ARL-CNS. The sensitivity, specificity and accuracy rate of the conventional sequence combined with SWI-ITSS were found to be 100%, 70.0%,and 84.2%, respectively. The sensitivity and accuracy of the conventional sequence combined with SWI were improved compared with the conventional sequence. However, the time required to scan the whole brain takes much longer, taking approximately 4 minutes. If every AIDS patient undergoes this sequence, it will undoubtedly cause great pressure to clinics and reduce work efficiency. Therefore,we recommend that when distinguishing ARL-CNS from toxoplasmosis or tuberculoma, this sequence should be scanned as soon as possible to obtain a correct diagnosis.
3.3 Shortcomings of this study
The sample size of the study was insufficient. The pathology results in the infection group were more and relativelycomplicated, which may have affected the determination of MR signs and the accuracy of the statistical results. The next step in this field of study is to increase investment in this research area to increase sample collection. In this way, more objective results can be obtained, leading to further clarity on the early clinical diagnosis of ARL-CNS.