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Radiographic
Radiographic Assessment of HIV-Associated Diseases
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Introduction
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Radiographic Findings for Specific Clinical Conditions
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transparent imagePulmonary Infections
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transparent imagePneumocystis jiroveci Pneumonia
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transparent imageMycobacterial Infections
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transparent imageFungi
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transparent imageCytomegalovirus
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transparent imageOther Organisms
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transparent imagePulmonary Neoplasms
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transparent imageKaposi Sarcoma
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transparent imageLymphoma
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transparent imagePrimary Lung Carcinoma
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transparent imageMiscellaneous Diseases
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transparent imageLymphocytic Interstitial Pneumonitis
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transparent imageLymphadenopathy Syndrome
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transparent imageImmune Reconstitution Inflammatory Syndrome
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transparent imageNonspecific Interstitial Pneumonia
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Gastrointestinal Radiographic Findings
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transparent imageHepatobiliary System
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transparent imageInfections
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transparent imageCandida
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transparent imageCytomegalovirus
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transparent imageCryptosporidiosis
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transparent imageMycobacterium avium Complex
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transparent imageMycobacterium tuberculosis
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transparent imageBacillary Angiomatosis
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transparent imageNeoplasms
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transparent imageKaposi Sarcoma
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transparent imageLymphoma
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Brain Imaging
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transparent imageInfections
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transparent imageToxoplasmosis
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transparent imageHIV Encephalitis and Leukoencephalopathy
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transparent imageCryptococcosis
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transparent imageTuberculosis
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transparent imageProgressive Multifocal Leukoencephalopathy
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transparent imageNeoplasms
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References
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Tables
Table 1.Common Pulmonary Radiographic Findings in HIV Disease and Associated Differential Diagnoses
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Figures
Figure 1.Non-Hodgkin Lymphoma, Initial Chest Radiograph
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Figure 2.Non-Hodgkin Lymphoma, Chest Radiograph 6 Weeks Later
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Figure 3.Cytomegalovirus Gastritis
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Figure 4.Non-Hodgkin Lymphoma, Bilateral Renal Masses
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Figure 5.Non-Hodgkin Lymphoma, Multiple Hepatic Masses
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Introduction
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This chapter addresses the main uses and findings of radiographic imaging for HIV-related disease. The role of imaging methods in the diagnosis of diseases associated with HIV infection depends on such factors as cost, availability, and expertise of the clinician or radiologist interpreting the image. For example, nuclear medicine scanning with gallium or high-resolution computed tomography (HRCT) is used in some medical centers to evaluate patients for Pneumocystis jiroveci pneumonia (PCP) whereas, in others, plain chest radiography is the method of choice, and more advanced imaging rarely, if ever, is requested. Although authorities may differ regarding the exact role of radiologic investigation in the evaluation of HIV-related pathology, many have reached similar conclusions about the strengths and weaknesses of different methods.(1)

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Radiographic Findings for Specific Clinical Conditions
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Pulmonary Infections
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Common HIV pulmonary radiographic findings and associated differential diagnoses are presented in Table 1.

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Pneumocystis jiroveci Pneumonia
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Although declining in incidence because of prophylactic measures, PCP remains one of the most frequently encountered opportunistic pneumonias in patients with advanced HIV disease.(2-4) Although the radiographic findings in patients with PCP vary, the majority of chest radiographs reveal bilateral, fairly symmetric, fine to medium reticular heterogeneous opacities.(5,6) As the disease worsens, the opacities coalesce and eventually appear as a bilateral homogeneous consolidation. Uncommonly, a more coarse reticular pattern or a miliary pattern may be noted.(7)

Unilateral or unilobar involvement may occur, but the radiographic pattern remains as fine reticular opacities. Predominant upper lobe involvement occurs with increased frequency in patients who have used aerosolized pentamidine for prophylaxis.(8,9) As the use of this form of prophylaxis has waned, the incidence of this appearance has decreased similarly. The presence of hilar or mediastinal adenopathy as well as pleural fluid is rare and should suggest another disease process. These findings usually are seen in patients who have been taking aerosolized pentamidine and have developed disseminated pneumocystosis.(10,11) Some cases of pneumocystosis following use of dapsone prophylaxis have been reported.(12) Calcified hilar and mediastinal lymph nodes rarely occur.(13)

Approximately 10% of patients with HIV disease and subsequently proven PCP have had normal chest radiographs. In some circumstances, gallium scanning or HRCT may demonstrate lung abnormalities, particularly ground-glass opacities on HRCT in these patients.(14) In many institutions, however, treatment is recommended empirically, without a request for further imaging.(15,16)

After appropriate therapy for PCP, radiographic studies reveal evidence of improvement within 10 days and subsequent complete resolution in most patients. However, radiographic improvement may lag behind clinical improvement by several days.(17) Also, abnormalities may be evident for a prolonged period, probably representing interstitial fibrosis.(18) Air-filled cystic spaces or pneumatoceles with thin walls are seen in 10% of HIV-infected patients with PCP,(19) and spontaneous pneumothorax occurs in 5%.(20,21) Resolution of the pneumatoceles may take several months. Focal nodules with or without cavitation represent another rare feature of PCP. Cavity walls usually are thicker and more irregular than pneumatocele walls.(22,23) Approximately 4 days after beginning intravenous trimethoprim-sulfamethoxazole therapy, patients may have chest radiographic findings that imply that their clinical condition has worsened. These findings may be attributable to pulmonary edema, which usually will resolve in 1-2 days with diuretic therapy and/or careful fluid management.

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Mycobacterial Infections
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Mycobacterium tuberculosis

M tuberculosis is an increasingly important infection in patients with HIV disease.(24) In recent years, the overall incidence of tuberculosis has risen, in part because of the HIV epidemic. Early in the course of HIV infection, radiographic findings for patients with pulmonary tuberculosis may be similar to those in persons with normal immune status: heterogeneous and occasionally cavitating lesions occur in the apical and posterior segments of the upper lobes and in the superior segment of the lower lobes. In patients with advanced HIV infection, the radiograph will not demonstrate cavitation or a tendency to localize in particular segments of the lung. Instead, diffuse, usually coarse, heterogeneous, reticular, and occasionally nodular opacities are noted in both lungs. Cavitation previously was thought to be related to CD4 lymphocyte count, but a recent study found that cavitation occurred in 65% of patients having chest films consistent with postprimary tuberculosis, independently of whether the CD4 count was greater than or less than 200 cells/µL.(25) This remains a contentious issue. Hilar or mediastinal adenopathy occurs in 25-90%, and pleural fluid may be present in approximately 20% of patients.(26) In patients with HIV disease, lymphadenopathy revealed by computed tomography (CT) most likely is related to mycobacterial causes.(27)

With appropriate therapy, radiographs reveal resolution in most patients with HIV disease and pulmonary tuberculosis. A lack of improvement, or radiographic evidence of deterioration, suggests the presence of other opportunistic infections.(28) In areas where drug-resistant tuberculosis is common, a change in therapy is warranted.(29) After beginning antiretroviral therapy (ART), some patients with AIDS and tuberculosis have experienced worsening of the chest radiographs. This is presumed due to a heightened immune response. The chest film may reveal increasing lymphadenopathy, lung opacities, and pleural fluid.(30,31) Another study found that patients on ART were more likely to present with a postprimary pattern than a primary pattern on chest films, presumably because of a heightened immune response.(32)

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Mycobacterium avium Complex

M avium complex (MAC) pneumonia is rare. Most patients with positive sputum culture simply are colonized. Radiographic evaluation of pulmonary MAC infection may reveal bilateral, diffuse, reticular, heterogeneous opacities. No specific distribution has been reported. Hilar and mediastinal adenopathy occurs in 6-20% of patients.(33,34) Cavitation and pleural fluid are rare.(35) Similar findings have been reported in children with MAC, with chest films demonstrating mediastinal adenopathy, cavitation, and bronchiectasis.(36) Chest radiographs frequently appear normal in HIV-infected patients with MAC pneumonia.(37)

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Other Mycobacterial Infections

A variety of mycobacterial organisms have been responsible for thoracic disease in HIV-infected patients. Mycobacterium kansasii may present with focal homogeneous opacities, or focal or diffuse heterogeneous opacities. Cavitation may occur. Lymphadenopathy is seen in up to 25% of patients. Pleural fluid is uncommon.(38) The features on chest imaging of other types of mycobacterial infections may overlap with those seen with tuberculosis.(39) An increasing number of unusual species have been reported. For example, Mycobacterium tilburgii has been reported to appear as localized lung disease in contrast to the disseminated pattern that had been described previously.(40)

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Fungi
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HIV-infected patients may become infected with fungi endemic to some parts of the world.(41,42) Chest radiographs of patients with histoplasmosis predominantly show bilateral, diffuse, coarse, nodular opacities. Other reported findings in patients with HIV disease and clinically proven histoplasmosis include alveolar consolidation, hilar adenopathy, cavitation, pleural fluid, and normal radiographic findings.(43-46)

Patients with advanced HIV disease who have lived in the southwestern United States, northwestern Mexico, or regions of Central and South America may develop systemic coccidioidomycosis, although the advent of effective ART may have led to a decline in incidence.(47) Chest radiographic findings in these patients include diffuse, coarse, nodular opacities that are indistinguishable from those associated with histoplasmosis and are similar to findings in some instances of tuberculosis in patients with advanced HIV disease. Other reported findings include cavitation and, in at least 1 case, CT evidence of hilar adenopathy.(48-51) In a large series of HIV-infected patients with coccidioidomycosis, 65% had diffuse reticulonodular disease, 14% had focal findings, and 16% had normal chest films.(52)

In HIV-infected patients, the findings of cryptococcal pulmonary infection may differ from those seen in nonimmunosuppressed individuals. Some studies have found more disseminated heterogeneous disease, but one report states that there is a higher likelihood of focal homogeneous opacities as well as a greater tendency toward lung nodules and masses.(53) Chest radiographic findings in patients with this infection most commonly include hilar and mediastinal adenopathy, and diffuse, often nodular, heterogeneous opacities. Larger, well-defined nodules and cavitary lesions also are common. In some patients, pleural effusion and miliary disease have been described.(54-57)

Numerous cases of invasive aspergillosis have been observed. Chest radiographic findings in these patients may include focal pneumonia, upper lobe cavitary disease, and bilateral reticular opacities.(58-60) Nodules, pleural effusion, and adenopathy also are reported, but occur less frequently.(61)

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Cytomegalovirus
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In most patients, cytomegalovirus (CMV) infection coexists with other opportunistic infections, particularly PCP. Controversy exists as to whether and to what extent CMV actually contributes to lung pathology.(62) One report states that positive immunostaining for CMV on bronchoalveolar lavage fluid may indicate a need for antiviral treatment.(63) Reliable diagnosis depends on demonstration of CMV inclusions on lung biopsy specimens.(64) In some patients with pathologically proven CMV pneumonia, chest radiographs show bilateral, reticular, interstitial disease. CT scans may reveal bilateral or focal heterogeneous opacities, ground-glass or consolidative changes, and, in many individuals, well-defined solitary or multiple nodules measuring up to 3 cm in diameter.(65) Differentiation of this infection from PCP on the basis of radiographic findings may not be possible.

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Other Organisms
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Conventional bacterial pneumonias occur with increased frequency in patients with advanced HIV disease, although the incidence has declined with the appropriate use of ART.(66) Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus are among the organisms responsible for these pneumonias. Chest radiographic examination in these patients usually reveals unilobar or multilobar air space consolidation (ie, the typical abnormality caused by these pathogens in non-HIV-infected persons). Other findings include parapneumonic effusions.(67) Clinical improvement usually is reflected radiographically within days following appropriate antibiotic treatment.

Nosocomial bacterial infections typically are caused by Pseudomonas aeruginosa, S aureus, and S pneumoniae and usually present with focal unilateral homogeneous opacities, but also may be diffuse and heterogeneous, or diffuse and homogeneous. Pleural effusions were seen in 10% of patients in one series.(68)

Bronchitis, often caused by the same organisms that cause pneumonia, occurs with increased frequency in patients with advanced HIV disease.(69) Manifestations include peribronchial thickening and tram tracking.(70) These findings are not typical of PCP, and may help to distinguish pyogenic infections from PCP. Bronchiectasis also is observed and is better appreciated with CT scanning.(71)

Nocardia infections have been reported in patients with HIV disease.(72) In one HIV-infected patient at San Francisco General Hospital, pulmonary Nocardia caused a homogeneous consolidation in the right middle lobe. Cavitation within areas of homogeneous consolidation also has been noted.(73) In a large series, chest radiographs revealed airspace opacities in 74% of patients and cavitation in 32%.(74)

Rhodococcus equi, a gram-positive bacillus, may cause large, fairly thick-walled cavities and empyema.(75) Lymphadenopathy also is reported.(76,77) CT and HRCT findings include homogeneous opacities with cavitation, ground-glass opacities, centrilobular nodules, and tree-in-bud opacities.(78)

Pulmonary toxoplasmosis is reported in patients with advanced HIV disease.(79-81) Radiography reveals poorly defined nodules scattered throughout the lungs of some patients,(82) and pleural fluid may be present.

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Pulmonary Neoplasms
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Kaposi Sarcoma
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The typical radiographic pattern observed in HIV-infected patients with Kaposi sarcoma (KS) consists of poorly defined nodular opacities approximately 1-2 cm in diameter scattered throughout both lungs. Coalescence of opacities to form homogeneous areas of consolidation is seen later in the course of disease. Also seen are diffuse, coarse, linear opacities, particularly in the perihilar and lower lung regions. Hilar adenopathy is demonstrated infrequently in patients with KS, but pleural fluid is observed in 35-50% of patients.

Development of KS generally is slow but, if hemorrhage occurs, the radiographic picture worsens rapidly.(83-85) The chest radiographic findings mentioned previously are virtually pathognomonic for KS, as is the appearance of intrabronchial lesions visualized by bronchoscopy, but nuclear radiology and CT scanning are used occasionally in diagnosis.(86,87) Usually, patients with KS exhibit KS-related radiographic changes late in the course of the disease, although pulmonary KS manifestations occurred before lymphocutaneous manifestations in a few reported cases.(88) Immune reconstitution inflammatory syndrome may lead to flaring of pulmonary KS.(89)

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Lymphoma
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In one series, intrathoracic involvement occurred in 10% of AIDS patients with non-Hodgkin lymphoma (NHL).(90) Abnormalities include pleural effusions, hilar and/or mediastinal lymphadenopathy, perihilar reticulonodular opacities, and well-defined, rapidly growing nodules measuring 0.5-5.0 cm in diameter (Figure 1 and Figure 2).(91-93) At least 1 of these large nodules cavitated after therapy. There is a report of a case of primary pulmonary lymphoma presenting with atelectasis of a lung.(94) The radiographic appearance of multicentric Castleman disease in patients with HIV infection reveals reticular and/or nodular heterogeneous lung opacities, mediastinal lymph node enlargement, and, less commonly, pleural effusion.(95)

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Primary Lung Carcinoma
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Although lung cancer has been described in patients with AIDS, it is controversial whether a cause-and-effect relationship exists.(96,97-99) One series included 22 young HIV-seropositive patients with lung cancer.(100) It is unclear whether these neoplasms are coincidental with HIV disease, or if they might be related to abnormal immune function. In another series, no difference in incidence of lung cancer in young patients was seen in pre- and post-AIDS era populations.(101) In another review, the authors concluded that, although AIDS patients present with lung cancer at an earlier age, a definite cause-and-effect link cannot be established.(102) A recent publication suggests that a higher risk of lung cancer in these patients may be due to a higher smoking prevalence.(103) Radiographic findings include mediastinal adenopathy, hilar and parenchymal masses, atelectasis, and pleural effusions.(104)

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Miscellaneous Diseases
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Lymphocytic Interstitial Pneumonitis
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Lymphocytic interstitial pneumonitis (LIP) is an index diagnosis of AIDS in the pediatric population. Chest radiographs reveal fine reticular or reticulonodular opacities in about one third of patients, coarse reticular opacities in about 12%, and combined heterogeneous and scattered homogeneous opacities in just over half.(105) The radiographic abnormalities remain stable throughout the course of HIV infection in 75% of patients. With time, lymphadenopathy may develop.(106) The chest radiographic appearance of LIP may be indistinguishable from that of PCP. CT demonstrates small nodules in a peribronchovascular distribution and ground-glass opacities.(107) HRCT may reveal perilymphatic and subpleural nodules when the chest film is normal.(108) Treatment with antiretroviral agents has produced a mixed response but certainly may lead to improvement in clinical and radiographic findings.(109,110)

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Lymphadenopathy Syndrome
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Patients with HIV-related lymphadenopathy syndrome usually show subdiaphragmatic lymphadenopathy and splenomegaly. No significant hilar or mediastinal adenopathy on chest radiographs or CT scans has been reported in patients with this syndrome alone. The presence of hilar or mediastinal adenopathy in a patient with HIV disease and the lymphadenopathy syndrome suggests the possibility of lymphoma, KS, tuberculosis, or fungal disease. Occasionally, chest radiography in these patients reveals an enlarged spleen. Abdominal or retroperitoneal lymph nodes with central necrosis on CT also are unlikely to be due to HIV lymphadenopathy syndrome. In some cases, needle aspiration or excisional biopsy may be necessary to rule out lymphoma, KS, mycobacterial disease, or other infection.

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Immune Reconstitution Inflammatory Syndrome
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When treated with effective ART, patients with previously quiescent opportunistic infections may demonstrate new or recurrent clinical and radiologic findings of disease.(111,112,113) This phenomenon has been reported with atypical mycobacteria, fungi, and viruses. Worsening of tuberculosis also may be noted.(114) Some cases of sarcoidosis beginning after initiation of ART have been recognized as well.(115) One case of cyst and nodule formation not associated with definite recurrent infection is reported in a patient with previous TB.(116)

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Nonspecific Interstitial Pneumonia
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In a review of 351 patients with HIV infection and presumed PCP, 67 patients were ultimately found not to have PCP. Sixteen of these patients had nonspecific interstitial pneumonia (NSIP). The diagnoses were not distinguishable based on clinical characteristics, although those with NSIP had higher CD4 counts. Interstitial opacities were the most common chest film finding in NSIP. In 6 patients these were diffuse, and in 8 they occupied fewer than 2 quadrants. One patient had diffuse alveolar opacities, and another had a normal film.(117)

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Gastrointestinal Radiographic Findings
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Patients with advanced HIV infection referred for radiographic examination of the gastrointestinal (GI) tract have a high incidence and a wide spectrum of abnormal findings. Although patients with endoscopically confirmed GI infections may have a normal-appearing barium study, in general, contrast radiography is relatively sensitive (but not specific) in the detection of GI infections and tumors. A potentially important observation is the existence of multifocal areas of involvement of the GI tract (eg, duodenum, plus small bowel or colon) in most patients with advanced HIV disease and GI pathology.(118) Multifocal abnormalities are uncommon in the general population, regardless of the nature of the GI pathology. In HIV disease, multiple foci of KS, widely distributed opportunistic infection, multiple opportunistic infections, coexistent tumor and infection, or even coexisting tumors (eg, KS and lymphoma) can cause multifocal abnormalities.(119)

The detection of multifocal GI abnormalities may be an important indicator of HIV infection in undiagnosed patients at risk for HIV. In patients already diagnosed with HIV infection, barium radiography of the GI tract helps to identify those individuals who might need endoscopy and to direct the selection of biopsy sites. Barium radiography also is valuable in detecting easily treatable non-HIV-related conditions, such as peptic ulcer disease, which may coexist with HIV infection. CT scanning may provide information about intraluminal as well as solid organ or lymph node disease. Ultrasound may be useful as an alternative modality when access to advanced imaging is limited.(120)

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Hepatobiliary System
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Infections of the liver and biliary system with any of a number of organisms may result in solitary or multiple hepatic abscesses or different forms of biliary involvement, including papillary stenosis and sclerosing cholangitis. Papillary stenosis will cause bile duct dilatation and delayed emptying of contrast into the duodenum; sclerosing cholangitis presents with focal strictures and dilatations of the intra- and extrahepatic bile ducts. Both forms of biliary disease may be seen at the same time, and occasionally long biliary strictures are noted. Liver disease may be diagnosed with CT or ultrasound; biliary disease may be diagnosed with CT, ultrasound, or endoscopic retrograde cholangiopancreatography (ERCP).(121,122)

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Infections
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Candida
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Candida albicans is the opportunistic organism that most frequently affects the GI tract in patients with HIV disease. The radiographic findings of Candida (monilial) esophagitis range from mild mucosal irregularity of the proximal to mid esophagus, to diffuse nodularity, a cobblestone appearance, extensive plaque formation, and occasional deep ulceration. Rare cases involve large fungus balls and bezoars. Invasive candidiasis can mimic primary or secondary tumor of the esophagus, causing luminal narrowing and masslike thickening of the esophageal wall.(118) Dissemination is unusual, but can lead to abscesses of the liver, spleen, or kidney.(123)

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Cytomegalovirus
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CMV and other herpesviruses can cause esophagitis that is radiographically indistinguishable from Candida infection on contrast-enhanced studies. More characteristic, however, are shallow ulcerations with a surrounding halo of edema or deep, longitudinally oriented ulcers. Nodular or vertical linear plaques are another manifestation. In some cases, the radiographic features of CMV gastritis (shallow ulcers and enlarged folds) are similar to those seen in other forms of gastritis (Figure 3).(124,125)

More commonly, CMV affects the small bowel and colon, causing disease that clinically, radiographically, and pathologically can simulate idiopathic inflammatory bowel disease or ischemic colitis.(126) Contrast-enhanced studies in patients with mild to moderate CMV colitis may reveal superficial erosions, granular mucosa, spasm, and prominent submucosal nodular indentations (2-4 mm), representing lymphoid nodular hyperplasia. In individuals with severe disease, studies may reveal frank ulceration, submucosal hemorrhage ("thumbprinting"), and perforation. The findings may be diffuse or focal; cecal involvement predominates in some series. CT scans typically reveal circumferential colonic wall thickening with submucosal edema and hypoattenuation. Usually the cecum and ascending colon are involved but other areas can be abnormal. Lymphadenopathy usually is not seen.(119)

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Cryptosporidiosis
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In patients with HIV disease and cryptosporidiosis, the radiographic manifestations on contrast-enhanced studies are nonspecific and varied, and range from diffuse, regular thickening of duodenal and jejunal folds to a more disorganized, irregular fold pattern. Increased secretions radiographically recognized as dilution and flocculation of the intraluminal barium often are evident in the small bowel and, less commonly, in the colon. CT scans may reveal similar findings of small intestine dilatation, wall thickening, and increased secretion.(127) Antral narrowing has been described when the stomach is involved.(128) Benign pneumatosis also has been reported.(129) Some investigators report a pattern of diffuse colitis when parasitic infestation has persisted for several months.(118,130)

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Mycobacterium avium Complex
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Patients with HIV disease have an increased incidence of infections with atypical mycobacteria, particularly MAC. Patients with disseminated MAC infection associated with HIV disease often complain of systemic and abdominal symptoms, particularly night sweats, abdominal pain, diarrhea, and weight loss. Clinicians often obtain barium studies of the GI tract and abdominal CT in this setting. The most common CT findings are enlarged retroperitoneal and mesenteric lymph nodes (42%), hepatomegaly (50%), splenomegaly (46%), and small bowel wall thickening (14%).(131)

Barium studies of the upper GI tract may reveal esophageal ulceration or small bowel pathologic changes marked by thickened, distorted folds and increased secretions.(132) Abdominal CT frequently (>80%) demonstrates large, bulky, retroperitoneal and mesenteric adenopathy.(133) The lymph nodes usually are clustered and uniform in attenuation value, in contrast to nodes in tuberculosis, which more frequently have low central attenuation and usually are larger.(134) Hepatomegaly may be present and severe,(127) and is more likely in MAC than in M tuberculosis disease.(134) In most cases, specimens obtained by CT-guided biopsy definitively show large, foamy macrophages filled with acid-fast bacteria. The intracellular, rodlike organisms also may stain positive with periodic acid-Schiff (PAS) stain. This latter feature, the clinical presentation, and radiographic and CT findings are similar to findings in Whipple disease, leading to the designation of abdominal MAC infection as "pseudo-Whipple disease," and suggesting that the gut may be one portal of entry in disseminated MAC.(135)

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Mycobacterium tuberculosis
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Esophagitis secondary to spread of M tuberculosis from mediastinal nodes may lead to barium radiographic and CT findings of extrinsic masses, ulceration, sinus tracts, and fistulous tracts. Tuberculous colitis occurs chiefly near the ileocecal region, and contrast-enhanced CT scans may reveal thickened bowel wall. Necrotic lymph nodes with low attenuation centers may be seen in association with tuberculosis.(127,134) A recent review states that lymph nodes with central low attenuation are more common, and that lymph nodes are larger (mean 4.0 cm vs 2.0 cm, respectively) with tuberculous involvement than with MAC.(134)

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Bacillary Angiomatosis
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This response to infection with Bartonella henselae and Bartonella quintana results in cutaneous and systemic hemangioproliferation, particularly in patients with very reduced CD4 counts. In lymph nodes, this results in hyperattenuation. In the liver, the disease is called peliosis hepatis and may appear as multiple blood-filled cysts. The spleen also may be involved with these low-attenuation lesions. If the cysts are larger than 2 cm, the differential includes bacillary angiomatosis and lymphoma. The combination of hyperattenuating lymph nodes, larger low-attenuation lesions in the liver and spleen, and severe decrease in CD4 counts suggests bacillary angiomatosis.(119)

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Neoplasms
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Kaposi Sarcoma
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Where effective ART is available, the incidence of KS and the outlook for affected patients has improved.(136) Early lymph node and visceral involvement are frequent in HIV-associated KS, especially in patients with advanced immunosuppression. Late in the course of HIV disease, lesions may involve virtually any organ system. Endoscopy reveals that nearly 50% of patients with mucocutaneous KS also have GI KS, although barium radiography reveals only a minority of these lesions.(137) KS can affect any part of the GI tract from the pharynx to the anus. Most persons with GI lesions are asymptomatic, although more advanced KS may involve GI bleeding, obstruction, perforation, and diarrhea. A case of intussusception from an ileal KS lesion has been reported.(138) The typical radiographic manifestations of GI KS are submucosal plaques, some with central ulceration ("target" or "bull's-eye" lesions). Larger polypoid masses are relatively common; circumferential and diffusely spreading lesions are rare.

Initial reports of CT findings in HIV-related KS emphasized the similarities with lymphadenopathy syndrome.(139) Splenomegaly and mild retroperitoneal and mesenteric nodal enlargement are common to both, and do not necessarily indicate widespread involvement with KS, particularly when the nodes are <1.5 cm in greatest diameter.

Bulky nodal enlargement, however, may be the only CT evidence of abdominal KS. KS-affected nodes may show significant contrast enhancement.(140) Bulky adenopathy in HIV-related KS cannot be distinguished radiographically from lymphoma or infections such as MAC, and further investigation by fine-needle aspiration biopsy may be necessary.(141)

Although the characteristic "target" lesions of KS seen on air contrast studies of the GI tract rarely are evident on CT studies, mural thickening may identify larger focal masses. The CT demonstration of focal small hepatic or splenic lesions of KS is uncommon. These lesions may show enhancement on delayed scans.(142)

As with KS in retroperitoneal nodes, KS in the liver or spleen has a nonspecific CT appearance, and biopsy may be necessary to distinguish it from other neoplastic or infectious causes. Usually, liver and spleen involvement consists of microscopic foci along vessels and is not visible radiographically. However, nonspecific hepatosplenomegaly may be seen in up to 41% of patients with KS.(119) Because KS can involve virtually any organ, it may produce unusual intraabdominal lesions that are readily detectable on CT and may be amenable to CT-guided biopsy. In our experience, fine-needle aspiration biopsy is reliable in diagnosing HIV-related KS. Stains of biopsy specimens show cohesive clusters of bland spindle cells arranged in characteristic slitlike spaces.

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Lymphoma
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In addition to KS, a variety of aggressive B-cell lymphomas are associated with HIV disease. To date, NHL has been the most common lymphoma in patients with advanced HIV disease. Hodgkin disease also can occur, however.

In some patients, the manifestations of lymphoma appear before those of advanced HIV disease. In a report of NHL in 90 homosexual men,(90) unique manifestations included a high prevalence of extranodal involvement in HIV-related lymphoma, which affected the brain and bone marrow, as well as abdominal, visceral, and mucocutaneous sites (Figure 4). Of the 90 patients, 88 had extranodal sites of involvement. In addition, patients with HIV-related lymphoma typically had highly malignant histologic subtypes and advanced stages of NHL.

A significant percentage of patients with HIV-related lymphoma demonstrate focal hepatic and splenic lesions (Figure 5). The liver and spleen usually are normal in size but may become enlarged if focal lesions are present.(143) In a series of 19 HIV-related lymphomas, 26% of patients with NHL had biopsy-proven focal hepatic lesions compared with 4-6% of patients without HIV disease.(144) In patients with relatively diffuse hepatic involvement of lymphoma, smaller microscopic foci (<1 cm) occasionally are difficult to recognize on contrast-enhanced CT images. Sonography can be useful in depicting disorganized hepatic echogenicity with small hypoechoic foci in patients with hepatomegaly and no obvious focal lesions on CT scans. Bulky retroperitoneal and mesenteric adenopathy is common. The nodes usually are of soft tissue opacity and do not tend to enhance with intravenous contrast as they do if the cause is KS.(140) In cases of enteric involvement, barium studies may reveal irregularly thickened gastric or intestinal folds.(127)

HIV-related Hodgkin disease appears to be substantially less common than HIV-related NHL. Features of Hodgkin disease, however, are distinctive in the population with HIV disease. Patients with HIV disease and Hodgkin disease typically present with stage III or IV Hodgkin disease, with mixed cellularity or nodular sclerosing histology. In addition, unusual manifestations of Hodgkin disease include involvement of the skin overlying the involved lymph nodes, and bone marrow involvement without splenic lesions. In a series of 10 patients with HIV-related Hodgkin disease studied at San Francisco General Hospital, 2 patients had bulky mesenteric nodal masses, an uncommon feature of Hodgkin disease in the non-HIV-infected population. In addition, CT scanning revealed noncontiguous sites of nodal involvement in which pelvic adenopathy occurred without periaortic involvement.

CT-guided percutaneous needle biopsy of enlarged lymph nodes can be very useful in diagnosing lymphoma. Although the technique requires considerable cytologic skill, the fine-needle biopsy has allowed diagnosis and subtyping of most HIV-related lymphomas in patients treated at San Francisco General Hospital.

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Brain Imaging
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In patients with advanced HIV disease, neurologic signs and symptoms are caused by a variety of central nervous system (CNS) infections, tumors, and direct effects of HIV on neural tissue. CT scanning and magnetic resonance imaging (MRI) are important tools for the early diagnosis and follow-up of treatment of these processes, although precise diagnosis remains difficult and the ultimate prognosis usually is grave.(145)

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Infections
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Toxoplasmosis
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The most frequent appearance of untreated Toxoplasma gondii encephalitis on CT scans consists of multiple deep and superficial lesions in both cerebral hemispheres, associated with edema and mass effect. The lesions characteristically are at the corticomedullary junction and in the basal ganglia.(146) The lesions typically are ring enhancing on contrast-enhanced CT or MRI.

The CT appearance of Toxoplasma encephalitis is not pathognomonic; for example, toxoplasmosis may be radiographically indistinguishable from primary CNS lymphoma. In many cases, CT imaging repeated after anti-Toxoplasma medication has been administered may assist diagnosis. If the lesion is due to Toxoplasma, serial CT scans show progressive diminution of contrast-enhanced lesions, edema, and mass within 2-4 weeks of treatment. Clinical improvement usually occurs within 1 week of initiating treatment. With continuous and long-term medical therapy, healing does occur, as evidenced by the return to normal of some scans and, on others, the appearance of areas of encephalomalacia. Because of persistent cellular immune defects in patients with HIV disease, however, this healing process may reverse when medical therapy is interrupted. CT scanning is a reliable indicator of recurrent lesions, which look the same as the original lesions. In one report, single photon emission computed tomography (SPECT)-thallium nuclear scanning was shown to differentiate toxoplasmosis (negative examination) from lymphoma (positive examination).(147) In some institutions, sequential thallium gallium scanning has been used to distinguish between toxoplasmosis and lymphoma.(148) If clinical status and CT scans fail to show a satisfactory response to medical therapy, biopsy of CNS lesions may be warranted.

MRI appears more sensitive than CT scanning in the detection of HIV-related CNS pathology.(149) If CT images fail to reveal a lesion accessible to biopsy sampling, then MRI is a useful adjunct. Some researchers believe that MRI is the method of choice for all HIV-related CNS pathology, and obviates CT scanning in most cases.

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HIV Encephalitis and Leukoencephalopathy
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Many instances of encephalitis and encephalopathy are direct or immunologically mediated results of HIV infection. Clinical manifestations of the AIDS dementia complex, including personality changes, confusion, memory loss, and motor deficits, develop over weeks to months. The most common CT finding in patients with HIV encephalitis is diffuse atrophy and sulcal dilatation.(150) CT scanning also may detect low-attenuation lesions in the white matter, although MRI is more sensitive in this regard.(150,151) MRI demonstrates increased signal on T2-weighted images in the periventricular white matter and centrum semiovale in patients with HIV encephalitis, and a diffuse increase in white matter signal intensity on long time of repetition (TR) images with HIV leukoencephalopathy.(152) No mass effect or enhancement of these lesions is demonstrated. Progressive atrophy is manifest on follow-up studies and reflects clinical deterioration. This correlation is not perfect, however, and some patients with clinical disease may have normal studies. Some investigators suggest that ART including zidovudine results in both clinical improvement and evidence of such improvement on MRI.(151,153) Although effective antiretroviral therapy reduces the frequency of many HIV-associated diseases, at least 1 autopsy study failed to find a decrease in HIV encephalopathy after effective ART became available.(154) MRI studies in a small number of patients receiving ART have shown that initial worsening on imaging may be followed by ultimate clinical improvement, and that the signal abnormalities may stabilize or even regress on subsequent examinations.(155) However, in another series of patients who experienced viral rebound on ART, a severe encephalopathy, perhaps related to the individuals' restored immune status, has been reported.(156)

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Cryptococcosis
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Cryptococcus neoformans is a common cause of opportunistic CNS infections in patients with AIDS. CT scanning may demonstrate nonspecific findings such as atrophy or hydrocephalus. MRI may demonstrate focal parenchymal cryptococcomas, cysts, miliary parenchymal disease, or dilated Virchow-Robin spaces.(157)

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Tuberculosis
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CNS tuberculosis may take several forms. Tuberculous meningitis occurs with greater incidence in areas where endemic tuberculous infections are frequent. CNS infection occurs without evidence of tuberculosis elsewhere in the body. Contrast-enhanced CT scanning demonstrates meningeal enhancement in the vicinity of the basal cisterns and over the cerebral cortex. Communicating hydrocephalus is relatively common and changes may be followed with CT scanning. Infarcts, most commonly in the distribution of the middle cerebral artery, also occur. Tuberculomas generally are seen in the supratentorial region, particularly frontal and parietal lobes in adults, and in the infratentorial region in children. Tuberculomas may be solitary or multiple, and contrast-enhanced CT scans may show ring enhancement with irregular walls. Edema often surrounds the lesions. Tuberculous abscesses are uncommon, may be solitary or multiple, and often are indistinguishable from pyogenic abscesses. Contrast enhancement of the walls is typical.(158)

MRI perhaps is more sensitive than CT for detecting tuberculous infection of the CNS. In tuberculous meningitis, gadolinium-enhanced T1-weighted images demonstrate meningeal enhancement in the basal cisterns, throughout the sulci, and over the convexity of brain. Other findings more likely to be detected by MRI than by CT include communicating hydrocephalus, tuberculomas, and infarct.

On MRI, tuberculomas demonstrate hypointensity relative to brain tissue on T1-weighted images and are hyperintense on T2-weighted images when the tuberculoma has a caseating liquid center. Tuberculomas with solid centers may reveal hypointense or isointense T1- and T2-weighted images. Gadolinium-enhanced T1-weighted images reveal rim enhancement, and lesions may be indistinguishable from pyogenic abscesses. Resolution of lesions can be verified with CT or MRI following antituberculous therapy.(159)

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Progressive Multifocal Leukoencephalopathy
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This CNS infection is caused by JC virus, an opportunistic human polyomavirus. Infection is characterized by several foci of white matter demyelination. Reactivation of virus in immunodeficient hosts may cause progressive multifocal leukoencephalopathy (PML). Clinically, patients present with altered mental status, personality changes, memory loss, or sensory abnormalities. Characteristically, CT scanning demonstrates 1 or more low-attenuation white matter lesions. Mass effect and contrast enhancement are not usual, but may occur.(160,161) MRI is more sensitive than CT in establishing the diagnosis. T2-weighted images demonstrate increased signal intensity in the periventricular and subcortical white matter. The parietooccipital and frontal lobes are more commonly involved. Bilateral involvement is common. MRI usually reveals isointense or hypointense T1-weighted images and increased signal intensity on T2-weighted images. Findings may be indistinguishable from those associated with HIV encephalitis, although the latter process is more often diffuse and periventricular, whereas PML is more commonly subcortical and focal,(151) and lesions of HIV encephalitis tend to be isointense on T1 images, whereas PML generally is hypointense. More recent work suggests that magnetic resonance spectroscopy and magnetization transfer imaging, a different type of MRI, may be better modalities for diagnosing and following this disease.(162) Effective ART has led to some improvement in morbidity and survival, but also has led in some instances to worsening secondary to presumed immune reconstitution inflammatory syndrome.(163)

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Neoplasms
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NHL is the most common neoplasm of the CNS in HIV patients, occurring almost exclusively in patients with advanced HIV disease. Symptoms include fever, weight loss, night sweats, seizures, headache, and confusion. Intracranial lymphoma generally is located centrally in the basal ganglia, thalamus, or corpus callosum. In up to one half of patients with CNS NHL, imaging reveals multiple lesions. In AIDS patients, lymphomas tend to be necrotic and many lesions are hypodense on CT images; ring enhancement of these lesions also may be noted. Differentiating lymphoma from toxoplasmosis may be extremely difficult. A trial of therapy for toxoplasmosis often is undertaken and follow-up CT images are obtained to see if the lesion has resolved. If no resolution is noted, biopsy may be necessary to exclude lymphoma or other infection. As noted above, SPECT-thallium nuclear scanning may differentiate toxoplasmosis (negative examination) from lymphoma (positive examination).(147) Sequential thallium gallium studies similarly are useful.(148) MRI findings of isointense or hypointense signal compared with brain parenchyma, on not only T1- but also T2-weighted images, are very suggestive of lymphoma. As necrosis occurs in the lesions, T2-weighted images may become slightly hyperintense. Gadolinium T1-weighted images demonstrate dense solid or ringlike enhancement.(147) There has been some work using magnetic resonance spectroscopy to distinguish between benign and malignant brain lesions, but its effectiveness for this purpose is questionable.(164) A recent review of several patients with lymphoma suggests that patterns are changing to include spontaneous hemorrhage, nonenhancing lesions, and diffuse white matter disease.(165)

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