Biomedical subjects

O Ganslandt

Publications and source records attributed to O Ganslandt.

At least 19 recordsLinked to original sources

PubMed2006

Intraoperative high-field MRI: anatomical and functional imaging.

Intraoperative high-field magnetic resonance (MR) imaging with integrated microscope-based navigation is at present one of the most sophisticated technical methods providing a reliable immediate intraoperative quality control. It enables intraoperative imaging at high quality that is up to the standard of up to date pre- and postoperative neuroradiological routine diagnostics. The major indications are pituitary tumor surgery and glioma surgery. In pituitary tumor surgery intraoperative MRI helps to localize hidden tumor remnants that would be otherwise overlooked. The same is true for glioma surgery, where the optimal extent of resection by simultaneous preservation of functional integrity can be achieved. This is possible since high-field MR imaging offers various modalities beyond standard anatomical imaging, such as MR spectroscopy, diffusion tensor imaging, and functional MR imaging which may also be applied intraoperatively, providing not only data on the extent of resection and localization of tumor remnants but also on metabolic changes, tumor invasion, and localization of functional eloquent cortical and deep-seated brain areas.

Brain Neoplasms↗

PubMed2006

Identifying the affected hemisphere by (1)H-MR spectroscopy in patients with temporal lobe epilepsy and no pathological findings in high resolution MRI.

Up to 30% of patients with temporal lobe epilepsy (TLE) remain without remarkable changes in MRI. In this study we investigated the role of (1)H-MR spectroscopy ((1)H-MRS) in lateralizing the affected hemisphere in the mentioned patient group. Twenty-two consecutive patients diagnosed with TLE were investigated by high resolution MRI and (1)H-MRS. We examined the incidence and diagnostic accuracy of temporal metabolite alterations determined by Linear Combination of Model Spectra (L C Model) via water reference. Metabolite values of each hemisphere of TLE patients were compared with healthy controls. Results of metabolite alterations were related to intensive video EEG focus localization. Reduction of N-acetylaspartate + N-acetylaspartyl-glutamate (tNAA) in the affected hemisphere revealed identification in six of nine patients (66%) with unilateral TLE. Group comparison revealed a significant reduction of tNAA (6.1+/-0.8*) in the involved temporal lobe compared with controls (6.67+/-0.4*, P=0.026). Choline levels were significantly increased in the affected hemisphere (1.42+/-0.17*) compared with healthy controls (1.22+/-0.17*, P=0.035). The results of our study show that (1)H-MRS is able to identify the affected hemisphere of MRI negative TLE patients and can be used as an additive tool in multimodal focus localization.

Adult↗

PubMed2005

Short TE single-voxel 1H-MR spectroscopy of hippocampal structures in healthy adults at 1.5 Tesla--how reproducible are the results?

The purpose of our study was to evaluate inter- and intra-subject variability and scan-rescan reproducibility of single-voxel 1H-MR spectroscopy (1H-MRS) in hippocampal structures at 1.5 T field strength. Thirty healthy adults were studied bilaterally by optimized, standardized short echo time single-voxel 1H-MRS (PRESS, TE=30 ms, TR=3000 ms, oblique voxel orientation, voxel size 2 cm3). Spectral analysis and absolute metabolite quantitation of N-acetylaspartate+N-acetylaspartyl-glutamate (tNAA), choline (Cho), creatine (Cr), total glutamate plus glutamine (Glu+Gln) and myo-inositol (Ins) were carried out by LCModel. Inter- and intra-individual reproducibility of these metabolite values were investigated by calculation of mean, standard deviation, coefficient of variation (CV), and by analysis of variance for repeated measurements. The smallest CV in intersubject variability was obtained for tNAA, followed by Cr, Cho, Ins and Glu+Gln. The results of the analysis of variance for repeated measures in inter-subject variability showed a marginal effect of scan repetition for Cr (p=0.063) and Glu+Gln (p=0.082); the rescan of both metabolites showed slightly higher concentrations. No statistical significant effect of scan repetition was seen for tNAA (p=0.913), Cho (p=0.857), and Ins (p=0.826). Rescan led to the same results and gave proof of good reproducibility. Scan-rescan testing in one subject showed comparable results: tNAA (CV=4.8%), followed by Cr, Ins, Glu+Gln and Cho (all CV above 10%).

Adult↗

PubMed2005

Visualization of the pyramidal tract in glioma surgery by integrating diffusion tensor imaging in functional neuronavigation.

OBJECT: The aim of this study was to investigate whether diffusion tensor imaging (DTI) can be integrated into functional navigation for the intraoperative visualization of the pyramidal tract. METHODS: A single-shot spin-echo diffusion-weighted echo planar imaging sequence on a 1.5 T magnetic resonance (MR) scanner was used for DTI. One null image and six diffusion-weighted images (high B value 1 000 mm/s (2)) were obtained. Color-encoded fractional anisotropy maps of the principal eigenvector rendered as a boxoid within each voxel were used for segmentation of the pyramidal tract. The segmented images were rigidly registered with a T(1)-weighted gradient echo 3D dataset for navigation in 16 patients with gliomas. In tumors adjacent to the motor cortex (n = 6) data from functional MR imaging were co-registered. RESULTS: The whole DTI processing lasted about 25-30 minutes in each case. In all cases DTI could be integrated into the navigational dataset resulting in an intraoperative visualization of the pyramidal tract by microscope-based navigation. Navigational accuracy measured as the target registration error was 1.2 +/- 0.46 mm. Registration of fractional anisotropy maps with the 3D navigational dataset was possible with an error of less than 2 mm. Co-registration with fMRI was consistent with DTI data. A neurological deterioration was observed only in one patient. CONCLUSIONS: DTI can be reliably integrated into navigational datasets. Thus, microscope-based neuronavigation can be used for an intraoperative visualization of the course of the pyramidal tract. However, a possible shifting of the pyramidal tract has to be taken into account after major tumor parts are removed.

Adolescent↗

PubMed2004

Functional neuronavigation and intraoperative MRI.

Our concept of computer assisted surgery is based on the combination of intraoperative magnetic resonance (MR) imaging with microscope-based neuronavigation, providing anatomical and functional guidance simultaneously. Intraoperative imaging evaluates the extent of a resection, while the additional use of functional neuronavigation, which displays the position of eloquent brain areas in the operative field, prevents increasing neurological deficits, which would otherwise result from extended resections. Up to mid 2001 we performed intraoperative MR imaging using a low-field 0.2 Tesla scanner in 330 patients. The main indications were the evaluation of the extent of resection in gliomas, pituitary tumours, and in epilepsy surgery. Intraoperative MR imaging proved to serve as intraoperative quality control with the possibility of an immediate modification of the surgical strategy, i.e. extension of the resection. Integrated use of functional neuronavigation prevented increased neurological deficits. Compared to routine pre- or postoperative imaging being performed with high-Tesla machines, intraoperative image quality and sequence spectrum could not compete. This led to the development of the concept to adapt a high-field MR scanner to the operating environment, preserving the benefits of using standard microsurgical equipment and microscope-based neuronavigational guidance with integrated functional data, which was successfully implemented by April 2002. Up to the end of 2002, 95 patients were investigated with the new setup. Improved image quality, intraoperative workflow, as well as enhanced sophisticated intraoperative imaging possibilities are the major benefits of the high-field setup.

Brain Neoplasms↗

PubMed2004

Magnetic source imaging supports clinical decision making in glioma patients.

OBJECTIVE: This study addresses the potential utility of preoperative functional imaging with magnetoencephalography (MEG) for the selection of glioma patients who are likely to benefit from resective surgical treatment regarding postoperative morbidity. METHODS: One hundred and nineteen patients with gliomas adjacent to sensorimotor, visual and speech related brain areas were investigated preoperatively with a MAGNES II biomagnetometer. In each patient the pre-surgical evaluation was focussed on the visual, sensorimotor cortex and/or of the speech related brain areas. A grading system was then used according to the distance of the MEG activation sources to the nearest tumour border to determine the further treatment. The therapeutic options consisted in conservative treatment, stereotactic biopsy and/or a radiation and chemotherapy, substantial cytoreduction and the gross total removal of the lesion. RESULTS: From 119 investigated patients, 55 patients (46.2%) were not considered for surgery due to tumour invasion to functional cortex. Sixty four patients (53.8%) were chosen for resective surgery. In the surgical group only four patients (6.2%) suffered from neurological deterioration. CONCLUSIONS: Magnetic source imaging (MSI) proved to be a valuable help in the clinical decision making process of lesions adjacent to functional important brain areas. The relative high number of patients in whom MSI warns of the postoperative crippling sequelae may lead to a better selection of patients who benefit from resective surgery. This method may help to find the patients for whom conservative treatment seems to be more favourable concerning quality of life in the surviving time.

Adolescent↗

PubMed2003

Glioma surgery evaluated by intraoperative low-field magnetic resonance imaging.

OBJECTIVE: To give an overview on intraoperative magnetic resonance (MR) imaging in glioma surgery. MATERIAL AND METHODS: MR imaging was performed using a 0.2T scanner, located in a radiofrequency-shielded operating theatre. Two setups were used: surgery either in a neighbouring operating theatre, or directly at the 5G line. Additionally, in gliomas adjacent to eloquent brain areas microscope- or pointer-based neuronavigation with integrated functional data was applied. 106 gliomas were among the 330 patients investigated in the last 5 years. RESULTS: We did not observe complications attributable to intraoperative MR imaging. Image quality was sufficient to evaluate the extent of the tumour resection in the majority of cases. Intraoperative imaging revealed remaining tumour in 63%. In a total of 26% patients further tumour could be removed due to the results of intraoperative imaging, increasing the rate of complete tumour removal especially in the low-grade tumours. The additional use of functional neuronavigation prevented an increased morbidity. CONCLUSION: Intraoperative MR imaging offers the possibility of further tumour removal during the same surgical procedure in case of tumour remnants, increasing the rate of complete tumour removal. The effects of brain shift can be compensated for using intraoperative image data for updating.

Adolescent↗

PubMed2003

Preliminary experience in glioma surgery with intraoperative high-field MRI.

OBJECTIVE: To apply a new setup, combining the benefits of high-field magnetic resonance imaging (MRI) with microscope-based neuronavigation, providing anatomical and functional guidance, in glioma surgery. MATERIAL AND METHODS: MR imaging was performed using a 1.5 T scanner, located in a radiofrequency-shielded operating theatre. The patient is lying on a rotating operating table, which is locked at the 160 degree position for surgery at the 5 G zone and turned into the scanner for imaging. The microscope, placed in the 5 G zone, in combination with a ceiling mounted navigation system enables microscope-based neuronavigation; integrated data from magnetoencephalography and functional MRI provide functional guidance. RESULTS: 126 patients were investigated with intraoperative high-field MRI, among them were 37 patients with gliomas. In the biopsy/catheter group (n = 8) MRI reliably depicted the needle position or the location of catheter placement. In the group with glioma resection (n = 29) intraoperative MRI revealed that the surgical objective was not achieved in 28%, leading to further tumour removal. We did not observe complications attributable to intraoperative high-field MRI. Image quality was not diminished by the operating room equipment, so that there was nearly no noticeable difference between pre- and intraoperative image quality. Neuronavigational guidance was applied in 31 patients: the integrated use of functional data prevented an increased morbidity despite extended resections. CONCLUSION: Intraoperative high-field MRI allows a reliable delineation of the extent of resection in glioma surgery. If the surgical objective was not met, a modification of the surgical strategy during the same operation is possible, thus leading to more radical resections. Furthermore, high-field MRI offers increased image quality and a much broader spectrum of different imaging modalities, compared to previous intraoperative low-field systems.

Adolescent↗

PubMed2003

Simple invasive fixation device for fractionated stereotactic LINAC based radiotherapy.

BACKGROUND: The aim of this study was to develop a relocatable fixation device for linear accelerator (LINAC) based fractionated stereotactic radiotherapy. METHOD: The device consists of a CT- and MRI-compatible stereotactic frame, monocortical titan bone screws, four frame-posts with a lock for the fixation pins and a modified head clamp with additional arms that allows the exact and rigid placement of the frame in the desired final position prior to the final placement of the bone screws. By simply disconnecting the lock from the posts, the frame can be dismounted after treatment planning and after each treatment session. The accuracy of reposition was assessed prospectively, using phantom studies and also by comparison of isocenter movements during fractionated radiotherapy in 10 patients with an intracranial lesion. FINDINGS: No adverse events were seen after the surgical procedure and the screws were well tolerated throughout the course of treatment. The mean isocenter shifts observed during phantom reposition studies were x=0.05 mm, y=-0.32 mm, z=0.18 mm and the mean isocenter shifts during fractionated treatment were x=0.67 mm, y=0.65 mm, z=0.44 mm. INTERPRETATION: This new fixation device provides excellent accuracy of reposition during stereotactic radiotherapy. It appears superior to non-invasive, mask fixation techniques. Safety margins as small as 1-1.5 mm may therefore be sufficient for this method of stereotactic radiotherapy.

Adult↗

PubMed2003

Image-guided removal of supratentorial cavernomas in critical brain areas: application of neuronavigation and intraoperative magnetic resonance imaging.

In a retrospective study the postoperative results of 26 patients operated on for supratentorial cavernous hemangiomas either deep-seated or near eloquent brain areas are summarized. An exact surgical approach to these lesions is essential to prevent neurological deterioration. Three different navigation systems were used and compared according to their clinical applicability. Complete removal of the lesion was obtained in all patients of this series. In six cases (23 %) functional data from magnetoencephalography or functional magnetic resonance imaging were integrated into the navigational setup. In 14 cases (54 %) intraoperative magnetic resonance imaging was performed. The follow-up time was 3 - 26 months (mean: 10 months). In the postoperative course one patient (3.8 %) developed a hemiparesis, another one developed quadrantopia. Nineteen patients presented with preoperative seizure history, 16 of these (84 %) had no further or rare seizures after surgery. The better results in seizure control were achieved in those patients with shorter duration of seizure history before surgery. The study indicates that the application of neuronavigation allows surgery on supratentorial cavernous hemangiomas in critical brain areas with low morbidity. The intraoperative visualization of eloquent cortex areas by integration of functional data allows a fast identification and exemption of eloquent brain areas, preventing neurological deterioration. Furthermore, the intraoperative MR resection control ensures a complete resection and illustrates the minimal invasive approach.

Adolescent↗

PubMed2003

Frameless stereotactic brain biopsy procedures using the Stealth Station: indications, accuracy and results.

This study presents the results of 57 stereotactic brain biopsies using a frameless neuronavigation system, the Stealth Station. The supratentorial lesions had a mean diameter of 33 mm and a mean distance of 32 mm from the entry point at brain surface. In all cases the stereotactic procedure was planned in the preoperative 3-D magnetic resonance data set. In seven cases additional data for identification of eloquent brain areas was integrated from magnetoencephalography or functional magnetic resonance imaging. During surgery the samples were sent to neuropathological examination and the operation completed after the confirmation of pathological tissue. Using this method, in 56 cases a pathological tissue was obtained and a diagnostic yield of 98% was achieved. In two cases (3.5%) a new neurological deficit remained (hemiparesis and visual field deficit). The mean operation time was 92 minutes including examination of frozen sections. The results of our series demonstrate, that frameless stereotactic systems can also be reliably applied for biopsy of supratentorial lesions larger than 15 mm. Frameless stereotaxy in combination with intraoperative pathological confirmation is a safe and reliable method for stereotactic brain biopsy with a diagnostic yield comparable to frame-based stereotaxy.

Adolescent↗

PubMed2002

Fractionated stereotactically guided radiotherapy of pharmacoresistant temporal lobe epilepsy.

PURPOSE: This prospective study evaluated the efficacy of fractionated stereotactically guided radiotherapy (SRT) as a treatment of pharmacoresistant temporal lobe epilepsy. PATIENTS AND METHODS: Inclusion criteria were patients aged between 17 and 65 years with unilateral temporal focus, without sufficient epilepsy control by antiepileptic drugs or neurosurgery. Two groups of 6 patients each were treated with 21 Gy (7 times 3 Gy) and 30 Gy (15 times 2 Gy). Study end points were change in seizure frequency, intensity, seizure length and neuropsychological parameters. RESULTS: All patients experienced a marked reduction in seizure frequency. The mean reduction of seizures was 37% (range 9-77%, i.e. seizures reduced from a monthly mean number of 11.75 to 7.52) at 18 months following radiation treatment and 46% (23-94%, i.e. 0.2-23 seizures per month) during the whole follow-up time. Seizure length was reduced in 5 out of 11 patients and intensity of seizures in 7 out of 11 patients. CONCLUSION: Radiotherapy was identified as a safe and effective treatment for pharmacoresistant epilepsy since a good reduction of seizure frequency during longer follow-up was observed. SRT means an appropriate alternative for patients with contraindication against neurosurgery or insufficient seizure reduction after neurosurgery.

Adolescent↗

PubMed2002

[Use of magnetoencephalography and functional neuronavigation in planning and surgery of brain tumors].

The role of magnetoencephalography (MEG) in neurology has been established for basic research, epilepsy, and functional brain mapping. The presurgical localization of functionally important brain areas has evolved as an important application of MEG. Both neurologists and neurosurgeons can use this method for decision-making and planning of nonsurgical or surgical treatment in brain tumors. The integration of functional brain mapping data into neuronavigation systems may help to minimize postoperative morbidity. This is especially important in low-grade gliomas, in which a potential benefit of surgery is only achieved when the tumor has been resected completely, whereas neurological deterioration means a substantial loss of quality of life during the survival time. This report addresses the utility of MEG combined with neuronavigation in the treatment of brain tumors adjacent to eloquent brain areas.

Adolescent↗

PubMed2002

Localisation of the sensorimotor cortex during surgery for brain tumours: feasibility and waveform patterns of somatosensory evoked potentials.

OBJECTIVE: Intraoperative localisation of the sensorimotor cortex using the phase reversal of somatosensory evoked potentials (SEPs) is an essential tool for surgery in and around the perirolandic gyri, but unsuccessful and perplexing results have been reported. This study examines the effect of tumour masses on the waveform characteristics and feasibility of SEP compared with functional neuronavigation and electrical motor cortex mapping. METHODS: In 230 patients with tumours of the sensorimotor region the SEP phase reversal of N20-P20 was recorded from the exposed cortex using a subdural grid or strip electrode. In one subgroup of 80 patients functional neuronavigation was performed with motor and sensory magnetic source imaging and in one subgroup of 40 patients the motor cortex hand area was localised by electrical stimulation mapping. RESULTS: The intraoperative SEP method was successful in 92% of all patients, it could be shown that the success rate rather depended on the location of the lesion than on preoperative neurological deficits. In 13% of the patients with postcentral tumours no N20-P20 phase reversal was recorded but characteristic polyphasic and high amplitude waves at 25 ms and later made the identification of the postcentral gyrus possible nevertheless. Electrical mapping of the motor cortex took up to 30 minutes until a clear result was obtained. It was successful in 37 patients, but failed in three patients with precentral and central lesions. Functional neuronavigation indicating the tumour margins and the motor and sensory evoked fields was possible in all patients. CONCLUSION: The SEP phase reversal of N20-P20 is a simple and reliable technique, but the success rate is much lower in large central and postcentral tumours. With the use of polyphasic late waveforms the sensorimotor cortex may be localised. By contrast with motor electrical mapping it is less time consuming. Functional neuronavigation is a desirable tool for both preoperative surgical planning and intraoperative use during surgery on perirolandic tumours, but compensation for brain shift, accuracy, and cost effectiveness are still a matter for discussion.

Adolescent↗

PubMed2002

Neuronavigation: concept, techniques and applications.

Neuronavigation provides intraoperative orientation to the surgeon, helps in planning a precise surgical approach to the targetted lesion and defines the surrounding neurovascular structures. Incorporation of the functional data provided by functional MRI and magnetoencephalography (MEG) with neuronavigation helps to avoid the eloquent areas of the brain during surgery. An intraoperative MRI enables radical resection of the lesions, the possibility of immediate control for tumor remnants and updates of neuronavigation with intraoperative images to compensate for brain shift. In this study, the experience of 432 patients undergoing neuronavigation assisted neurosurgical interventions using either the pointer-based or microscope-based navigational systems at the University of Erlangen-Nuremberg, Germany is presented. The procedures included stereotactic biopsy (n=53), stereotactic cyst puncture/ventricular drainage (n=15), eloquent cortex/tumor localization to facilitate tumor resection, assessment of neurovascular structures in the vicinity of tumors of the sellar-suprasellar regions, skull base, posterior fossa and ventricular region (n=252), and, surgery for epilepsy (n=9). Functional brain mapping using fMRI and MEG and their integration with neuronavigation was carried out in 24 and 128 patients respectively. The simultaneous use of intraoperative MRI to look for the remaining tumor was done in 159 patients and the update of navigational data was carried out in 17 patients. The mean system accuracy obtained by using both the fiducial registration as well as anatomical landmark-surface fitting computer algorithm was 1.81 mm. This study reviews the relative merits and demerits of the pointer and microscope based navigational systems and also highlights the role of functional brain mapping and intraoperative MRI, when integrated with neuronavigation, in the surgical decision-making to offer the chances of more radical resections with minimal morbidity.

Adolescent↗

PubMed2001

A combined study of tumor-related brain lesions using MEG and proton MR spectroscopic imaging.

The purpose of this study is to localize, in cases of brain tumors, pathological magnetic brain activities and to analyze metabolic alterations in functionally abnormal lesions using magnetoencephalography (MEG) and proton magnetic resonance spectroscopic imaging (1H MRSI). The study focused on 10 healthy volunteers and seven patients with common brain tumors, namely astrocytic tumor and meningioma. In spontaneous MEG, the pathological brain activities (slow, fast waves and spikes) were localized using a single equivalent dipole model. After the results of MEG and 1H MRSI were superimposed onto the corresponding MR images, the signal intensities of spectroscopically visible metabolites were analyzed in the regions where the dipoles of the pathological activities were concentrated. Increased slow wave activity was observed in four cases and fast wave or spike activity was significantly increased in one case. These pathological activities were localized in surrounding regions of the bulk of tumors, where mild reduction of N-acetyl aspartate (NAA) and slight accumulation of lactate (Lac) consistently existed. Preserved cortical areas, which are indicated by residual NAA, might be able to generate pathological magnetic activities under lactic acidosis. Such areas could be understood as a border zone between normal and seriously damaged brain tissue by tumors or associated brain edema. This combined technique with the different modalities gives insight into functional as well as metabolic aspects of pathological brain conditions.

Adult↗

PubMed2001

New approach to localize speech relevant brain areas and hemispheric dominance using spatially filtered magnetoencephalography.

We used a current localization by spatial filtering-technique to determine primary language areas with magnetoencephalography (MEG) using a silent reading and a silent naming task. In all cases we could localize the sensory speech area (Wernicke) in the posterior part of the left superior temporal gyrus (Brodmann area 22) and the motor speech area (Broca) in the left inferior frontal gyrus (Brodmann area 44). Left hemispheric speech dominance was determined in all cases by a laterality index comparing the current source strength of the activated left side speech areas to their right side homologous. In 12 cases we found early Wernicke and later Broca activation corresponding to the Wernicke-Geschwind model. In three cases, however, we also found early Broca activation indicating that speech-related brain areas need not necessarily be activated sequentially but can also be activated simultaneously. Magnetoencephalography can be a potent tool for functional mapping of speech-related brain areas in individuals, investigating the time-course of brain activation, and identifying the speech dominant hemisphere. This may have implications for presurgical planning in epilepsy and brain tumor patients.

Adult↗

PubMed2001

Correlation of sensorimotor activation with functional magnetic resonance imaging and magnetoencephalography in presurgical functional imaging: a spatial analysis.

In this study we investigated the spatial heterotopy of MEG and fMRI localizations after sensory and motor stimulation tasks. Both methods are frequently used to study the topology of the primary and secondary motor cortex, as well as a tool for presurgical brain mapping. fMRI was performed with a 1.5T MR system, using echo-planar imaging with a motor and a sensory task. Somatosensory and motor evoked fields were recorded with a biomagnetometer. fMRI activation was determined with a cross-correlation analysis. MEG source localization was performed with a single equivalent current dipole model and a current density localization approach. Distances between MEG and fMRI activation sites were measured within the same anatomical 3-D-MR image set. The central region could be identified by MEG and fMRI in 33 of 34 cases. However, MEG and fMRI localization results showed significantly different activation sites for the motor and sensory task with a distance of 10 and 15 mm, respectively. This reflects the different neurophysiological mechanisms: direct neuronal current flow (MEG) and secondary changes in cerebral blood flow and oxygenation level of activated versus non activated brain structures (fMRI). The result of our study has clinical implications when MEG and fMRI localizations are used for pre- and intraoperative brain mapping. Although both modalities are useful for the estimation of the motor cortex, a single modality may err in the exact topographical labeling of the motor cortex. In some unclear cases a combination of both methods should be used in order to avoid neurological deficits.

Adolescent↗