S. Herminghaus

Clinical application of proton magnetic resonance spectroscopy in the diagnosis of intracranial mass lesions

Diagnosis of primary and secondary brain tumours and other focal intracranial mass lesions based on imaging procedures alone is still a challenging problem. Proton magnetic resonance spectroscopy (1H-MRS) gives completely different information related to cell membrane proliferation, neuronal damage, energy metabolism and necrotic transformation of brain or tumour tissues. Our purpose was to evaluate the clinical utility of 1H-MRS added to MRI for the differentiation of intracranial neoplastic and non-neoplastic mass lesions. 176 mostly histologically verified lesions were studied with a constant clinically available single volume 1H-MRS protocol following routine MRI. 12 spectra (6.8%) were not of satisfactory diagnostic quality; 164 spectroscopic data sets were therefore available for definitive evaluation. Our study shows that spectroscopy added to MRI helps in tissue characterization of intracranial mass lesions, thereby leading to an improved diagnosis of focal brain disease. Non-neoplastic lesions such as cerebral infarctions and brain abscesses are marked by decreases in choline (Cho), creatine (Cr) and N-acetyl-aspartate (NAA), while tumours generally have elevated Cho and decreased levels of Cr and NAA. Gliomas exhibit significantly increased Cho and lipid formation with higher WHO tumour grading. Metastases have elevated Cho similar to anaplastic astrocytomas, but can be differentiated from high-grade gliomas by their higher lipid levels. Extra-axial tumours, i.e. meningiomas and neurinomas, are characterized by a nearly complete absence of the neuronal marker NAA. The additive information of 1H-MRS led to a 15.4%-higher number of correct diagnoses, to 6.2% fewer incorrect and 16% fewer equivocal diagnoses than with structural MRI data alone.

Brain metabolism in Alzheimer disease and vascular dementia assessed by in vivo proton magnetic resonance spectroscopy

Proton magnetic resonance spectroscopy (MRS) allows the assessment of various cerebral metabolites non-invasively in vivo. Among 1H MRS-detectable metabolites, N-acetyl-aspartate and N-acetyl-aspartyl-glutamate (tNAA), trimethylamines (TMA), creatine and creatine phosphate (tCr), inositol (Ins) and glutamate (Gla) are of particular interest, since these moieties can be assigned to specific neuronal and glial metabolic pathways, membrane constituents, and energy metabolism. In this study on 94 subjects from a memory clinic population, 1H MRS results (single voxel STEAM: TE 20 ms, TR 1500 ms) on the above metabolites were assessed for five different brain regions in probable vascular dementia (VD), probable Alzheimers disease (AD), and age-matched healthy controls. In both VD and AD, ratios of tNAA/tCr were decreased, which may be attributed to neuronal atrophy and loss, and Ins/tCr-ratios were increased indicating either enhanced gliosis or alteration of the cerebral inositol metabolism. However, the topographical distribution of the metabolic alterations in both diseases differed, revealing a temporoparietal pattern for AD and a global, subcortically pronounced pattern for VD. Furthermore, patients suffering from vascular dementia (VD) had remarkably enhanced TMA/tCr ratios, potentially due to ongoing degradation of myelin. Thus, the metabolic alterations obtained by 1H MRS in vivo allow insights into the pathophysiology of the different dementias and may be useful for diagnostic classification.

Preoperative Proton-MR Spectroscopy of Gliomas – Correlation with Quantitative Nuclear Morphology in Surgical Specimen

A comparison between data from proton-MR spectroscopy (1HMRS) and quantitative histomorphology of tumor cell nuclei in gliomas has not been reported up to now. Therefore, the question must be answered, if there are any significant correlations between histomorphology of gliomas and quantitative data from 1HMRS concerning tissue metabolites.Surgical glioma specimen (glioblastomas, astrocytomas, oligodendrogliomas) from 46 patients with tumor grades II–IV according to WHO have been evaluated by means of a digital image analysis system using Ki-67-immunostained paraffin sections. Nuclear density, Ki-67-proliferation index, nuclear area and shape variables (roundness factor, Fourier-amplitudes) have been determined from 200 randomly selected tumor cell nuclei in each tumor specimen. These data have been correlated with preoperative data from 1HMRS.A positive correlation between Fourier-amplitudes, choline peak and lipide peak was observed, as well as a negative correlation between these variables and the nuclear roundness factor. This result indicates higher choline and lipide peaks with increasing irregularity of nuclear outlines. Proliferation index Ki-67 was positively correlated with the lipide peak, nuclear density showed a positive correlation with the choline peak. Glioblastomas (n = 29) showed an additional positive correlation between mean nuclear size and total creatine. Anaplastic gliomas (n = 12) showed a positive correlation between lactate peak and the standard deviation of the nuclear roundness factor. Further multivariate analyses have shown, that for the present collective of 46 cases, histometric variables have a higher significance than spectroscopic data for the differentiation of the different tumor grades.These results verify a significant correlation between preoperative data from 1HMRS and histomorphology of tumor cell nuclei in gliomas, supporting the biological significance of both histomorphometry and 1HMRS for the evaluation of these tumors.

Diagnostic impact of proton MR-spectroscopy versus image-guided stereotactic biopsy.

SummaryBackground. The aim of this study was to compare the diagnostic accuracy of 1H MR-spectroscopy versus image-guided stereotactic biopsy.Method. A cohort of 83 consecutive patients with a broad spectrum of brain lesions were examined. Prior to stereotactic biopsy, the patients were subjected to 1H MR-spectroscopy examination. Diagnostic accuracy of 1H MR-spectroscopy and image guided stereotactic biopsy was determined for the largest diagnostic subgroups. Each diagnostic procedure was tested for concordance in every subgroup.Findings. The subgroups of patients comprised: low grade glioma, high grade glioma (grades III and IV), lymphoma and metastasis. For the sensitivity of 1H MR-spectroscopy ranged from 87.7 in high grade glioma to 92.3% in metastasis and for specificity from 93.3% for high grade glioma to 100% in low grade glioma. The highest positive predictive value of 100% was reached in the subgroup of low grade glioma. The highest negative predictive value was reached in lymphoma and metastasis, 100%. The kappa values were highly significant for all comparisons (p<0.001). The co-efficient ranged from 0.68 to 0.84. It was lowest in assessing high grade glioma and highest in lymphoma.Conclusion. Compared with each other 1H MR-spectroscopy and image-guided stereotactic biopsy showed a moderate to good, statistically highly significant concordance. In patients in whom operation is at an increased risk e.g., due to severe medical illness, 1H MR-spectroscopy as a noninvasive procedure may be sufficient to assess the diagnosis.

Morphology of proliferating and non-proliferating tumor cell nuclei in glioblastomas correlates with preoperative data from proton-MR-spectroscopy.

In contrast to the growing interest in proton‐MR‐spectroscopy (1HMRS) for preoperative examination of patients with brain tumors, there is nearly no knowledge about a correlation between data from 1HMRS and histomorphology as confirmed by quantitative morphological methods. Whether a correlation can be confirmed between data from 1HMRS and quantitative histomorphology of glioblastomas representing the most frequent type of brain tumors was investigated in the present study. Furthermore, it was of interest, whether correlations between spectroscopic data and histomorphology can be confirmed for proliferating and non‐proliferating tumor cell nuclei independently. Using stringent inclusion criteria for this study, 24 patients were investigated by means of preoperative 1HMRS and by means of digital image analysis of paraffin sections from the surgical specimen. Proliferating and non‐proliferating tumor cell nuclei were investigated separately in the region with the highest proliferative activity in each tumor using immunohistological staining for the proliferation marker Ki67. Main results showed highly significant correlations between total creatine and variables of nuclear size, as well as correlations between choline and variables of nuclear shape. These results were confirmed for both proliferating and non‐proliferating tumor cell nuclei. A significant correlation between N‐acetyl‐aspartate level and topometric variables (number of neighbors per nucleus, variables describing distances between tumor cell nuclei) was confirmed for proliferating tumor cell nuclei. Discriminant analysis provided a good separation of cases with high and with low values for these spectroscopic variables based on histomorphometric data. In conclusion, the results confirm a direct correlation between data from preoperative 1HMRS and histomorphological characteristics of glioblastomas supporting the biological relevance of spectroscopic data for the examination of brain tumor patients.

Grundlagen der 1H-MR-Spektroskopie intrakranieller Tumoren

ZusammenfassungDiagnostische Wertigkeit: Werden definierte Qualitätsstandards bei der Festlegung des Messvolumens und der lokalen Feldhomogenität eingehalten, kann die 1H-MR-Spektroskopie als sehr nützliches Werkzeug zur Diagnostik und Verlaufskontrolle intrakranieller Tumoren eingesetzt werden. Mit der 1H-MR-Spektroskopie gelingt in der Regel eine Differenzierung zwischen hirneigenen Tumoren und Metastasen. Zudem ist eine relativ zuverlässige Graduierung der Gliome möglich. Andere Kontrastmittel aufnehmende Läsionen wie akute Entzündungen können von Tumoren unterschieden werden. Problematisch ist allerdings die eindeutige Differenzierung verschiedener Gliome gleicher Graduierung. Bei kleinen Volumina (≤1,5 ml) sind für ein ausreichendes Signal-Rausch-Verhältnis sehr lange, im klinischen Routinebetrieb nicht akzeptable Messzeiten erforderlich. Künftige Entwicklungen: Die Einführung von 3-T-MR-Geräten, der Einsatz von Mehrkanaloberflächenspulen und schnellen MRS-Sequenzen werden zu einer erheblichen Verkürzung der Untersuchungszeit bei gleichem Signal-Rausch-Verhältnis führen. Insbesondere die Messzeit für die spektroskopische Bildgebung wird so weit reduziert werden können, dass sie zukünftig in Standarduntersuchungsprotokolle integriert werden kann. Für die Interpretation der gewonnenen Spektren sollte auf größere Datenbanken zurückgegriffen werden. Dies gilt vor allem, wenn die Diagnose nicht auf der Änderung eines einzelnen Signals, sondern des spektralen Musters beruht (d. h. einer spezifischen gleichzeitigen Änderung mehrerer Signale).AbstractDiagnostic Potential:1H-MR spectroscopy provides a useful tool for diagnosis and follow-up of intracranial tumors if defined standards regarding the determination of the region of interest and local homogeneity of the magnetic field can be accomplished. Often, 1H-MR spectroscopy enables differentiation of gliomas from metastasis. In addition, grading of gliomas is quite reliable. Other lesions with enhancement of contrast media like infections can be distinguished as well, while differentiation of various gliomas with the same grading is demanding. For small lesions (≤ 1.5 ml), the signal-to-noise becomes a limiting factor requiring examination times inapplicable for clinical use. Future Developments: Introduction of 3T-MR scanners, use of phased array surface coils, and fast MRS sequences will further reduce the time for spectroscopic examinations without a significant loss of the signal-to-noise ratio. This is crucial for application of spectroscopic imaging techniques, where the required measurement time has to be cut to a level which allows integration of this procedure in routine imaging protocols. In any case, substantial databases are required for interpretation of spectra, especially if the diagnosis is rather based on pattern analysis (i. e. simultaneous change of several metabolites) than on the intensity change of a single metabolite signal.

99mTC-HMPAO-SPECT and Proton MR Spectroscopy in the Diagnosis of Alzheimer's Disease

This ongoing study evaluated the diagnostic accuracy of HPAO-SPECT and 1HMRS in the diagnosis of Alzheimers disease. Both methods proved highly specific for diagnosis but post mortem validation of the clinical diagnosis is required for a final judgement on 1HMRS and HMPAO-SPECT.

Cutoff value of choline concentration reliably reveals high-grade brain tumors among other contrast-enhancing brain lesions.

BACKGROUND AND AIM To evaluate whether there is a cutoff value for a metabolite concentration measured by 1 H MR spectroscopy (MRS), which can be used to differentiate malignant brain tumors (high-grade gliomas, primary CNS lymphomas [PCNSL] and metastases) from other contrast-enhancing lesions like low-grade gliomas and non-neoplastic lesions. MATERIAL AND METHODS 1 H MRS was performed in 252 consecutive patients with space-occupying brain lesions which were enhanced with application of a contrast agent. Concentrations of N-acetyl-aspartate, total creatine, choline containing metabolites (total choline, tCho), lipids, and lactate were evaluated from the contrast-enhancing part of the lesions and from the normal appearing brain tissue. Linear discriminant analysis was used to find the best predictor for malignant brain tumors. In addition, receiver operating characteristic analysis (ROC) was performed to determine a cutoff value for the best predictor in detecting malignant brain tumors with a specificity of >95%. RESULTS All brain tumors and 20 out of 47 nonneoplastic lesions were examined histopathologically. The remaining 27 diagnoses were based on MR imaging, clinical findings, and follow-up. The final diagnosis was 134 high-grade gliomas (WHO grade III/IV), 36 metastases, 9 PCNSL, 8 low-grade gliomas (WHO grade I/II), 34 infections, 9 infarctions, 2 hematomas, and 2 vasculitides. 18 patients were excluded due to insufficient spectral quality. The tCho concentration was the best predictor to differentiate malignant brain tumors from enhancing low-grade gliomas or non-neoplastic lesions (F=26.6 [df: 25.833], p<0.0005). The ROC revealed that a cutoff tCho value, based on an increase of ≥40% compared to normal, yielded a specificity of 100% and a sensitivity of 89.4% to correctly diagnose a malignant brain tumor. CONCLUSION 1 H MRS reliably differentiates malignant brain tumors from other contrast-enhancing brain lesions. At least a 40% increase of tCho compared to normal brain tissue indicates a malignant tumor (WHO grade III/IV gliomas, PCNSL, metastases) with >90% specificity and sensitivity.

Functional Imaging during Olfactory Stimulation

We used fMRI to stimulate healthy volunteers with two different purely olfactory odorants to identify neocortical olfactory projections. For both substances activation was found in the superior temporal sulcus, frontal insular cortex, inferior frontal gyrus, orbitofrontal cortex, opercular part of the precentral gyrus and in the temporal pole.

Stereotactic Biopsy versus Proton Spectroscopy in the Diagnosis of Malignant Gliomas

We assessed the value of 1HMRS in the diagnosis of astrocytomas and glioblastomas compared with stereotaxic biopsy. 1HMRS is an alternative non-invasive diagnostic tool to predict the presence of malignant gliomas.